INHIBITORS OF CATALYTIC ANTIBODIES

Abstract: Specific, selective inhibitors of catalytic antibodies both synthetic and naturally occuring, their use and compositions thereof are disclosed. In particular, an inhibitor preventing the hydrolysis of the peptide bond between amino acid residues 16 and 17 in the neurotransmitter vasoactive intestinal peptide (VIP) by an anti-VIP catalytic autoantibody is disclosed.

Description: INHIBITORS OF CATALYTIC ANTIBODIES 1 FIELD OF THE INVENTION This invention pertains generally to substances capable of inhibiting catalytic antibodies and more particularly to substances capable of inhibiting naturally occurring catalytic autoantibodies. Several publications are referenced in this application by Arabic numerals within parentheses in order to more fully describe the state of the art to which this invention pertains. Full citations for these references are found at the end of the specification immediately preceding the claims and the disclosures of these publications are expressly incorporated herein by reference. BACKGROUND OF THE INVENTION The nature of the forces involved in ligand binding by antibodies and substrate binding by enzymes is similar, viz., hydrogen bonding, electrostatic interaction and hydrophobic effect. The energy obtained from enzyme-substrate binding may be visualized to force electronic strain in the substrate and facilitate the formation of a transition state. There is strong evidence for the theory that enzymes bind the transition state of the reaction they catalyze better than the ground state, resulting in a reduced free energy of activation for the reaction (1) . This has come to be known as the transition state theory of enzymatic catalysis. Other factors that may facilitate enzymatic catalysis are the proximity and orientation effects - apposition of correctly oriented reactants within the active site of the enzyme would reduce the requirement for a large number of random collisions prior to a productive reactant interaction. In principle, antibodies could catalyze chemical reactions by similar means. The first report of chemical conversion of a ligand by an antibody appeared in 1980 (2) , but the steroid ester hydrolysis by a rabbit polyclonal antiεerum described in this report was stoichiometric rather than catalytic. Subsequently, antibodies have been demonstrated to catalyze or facilitate chemical reactions, including acyl transfer (3), pericyclic (4) and redox reactions (5) . It is generally believed that these antibodies obtain their catalytic properties, like enzymes, from their ability to bind the transition state of the ligand better than its ground state. The known catalytic antibodies include tl. '≤e generated by immunization with selected epitopes as described above, and those which have been shown to occur naturally (6) . These naturally occurring antibodies are produced by an animal's immune system to the animal's own cellular component (self-antigen) , hence "autoantibodies", as opposed to antibodies elicited with an antigen introduced by specific immunization against a target antigen, and are known to enhance the rate of a chemical reaction, e.g., the cleavage of a peptide bond. Antibodies with enzymatic activity offer the possibility of specific, high efficiency catalytic chemical conversion of ligands. Many biological mediators are peptides or proteins, including the antigens, of pathogenic organisms, hormones, neurotransmitters and tumor specific antigens. It should be possible to utilize the vast repertoire of specificities that the immune system encompasses to catalyze chemical reactions not within the scope of naturally occurring enzymes. The combination of antibody specificity with the catalytic power of enzymes has the potential of generating potent therapeutic agents, e.g., catalytic antibodies capable of specifically hydrolyzing key viral coat proteins, tumor specific proteins, or endogenous proteins involved in disease. The utilization of these catalytic antibodies in medicine and industry would be greatly enhanced if a specific, selective method of inhibiting the activity of these antibodies were also available. For example, such inhibition could be useful in the treatment of autoimmune diseases. It is well known that certain autoimmune diseases are associated with autoantibodies directed against hormones and cell surface antigens. Examples of these diseases and associated autoantibodies are: Disease ., Autoantibodv to Diabetes Insulin, Insulin receptor Myasthenia gravis acetylcholine receptor Graves disease thyroid stimulating hormone receptor Systemic lupus erythematous small nuclear RNA, DNA, histones Pernicious anemia Intrinsic factor of Castle, gastric parietal cell antibodies It is known to treat autoimmune diseases generally by means of non-specific anti-immune treatments. These known treatments include steroids, alkylating agents, radiation, plas aphoresis, and surgical removal of the spleen. Each of these treatments suffers from many disadvantages well known in the art such as impairment of the patient's immune system. Since catalytic autoantibodies are likely to cause more harm than non-catalytic antibodies, it is now believed that the autoimmune diseases are caused by catalytic autoantibodies directed against nucleic acids, key regulatory peptides and proteins (e.g., insulin, glucagon, prolactin, VIP, substance P, blood clotting factors) and the cell surface receptors for these agents. For example, asthma is believed to be caused by a deficiency of vasoactive intestinal peptide (VIP) . VIP is a 28 amino acid peptide originally isolated from the intestine but now recognized to be a neuropeptide widely distributed in the central and peripheral nervous systems. There is evidence that VIP is a neurotransmitter in its own right. In addition, VIP may modulate neurotransmission by classical transmitters and has been implicated in regulation of blood pressure, bronchial tone, neuroendocrine activity and exocrine secretion. VIP appears to be the major neurobronchodilator in humans and a diminished influence of VIP on the airways may permit a dominance of constrictor influences, and may underlie airway hyperactivity in as. aa. VIP belongs to a family of structurally related peptides, other prominent members of which are peptide histidine isoleucine (PHI) , growth hormone releasing factor (GRF) and secretin. Like the peptides themselves, there is evidence that the receptors for VIP, GRF, PHI and secretin are related. Receptors for VIP are found in lung, vascular smooth muscle, brain, pancreas, skin, intestine and other tissues. The amino acid sequence of VIP is as follows: H S D A V F T D N Y T R L R K Q M A V K Y L N S I L N- NH 2 . It has been discovered that VIP binding antibodies exist in human circulation (7-9). Immunoprecipitation with anti-human IgG as well as chromatography on DEAE-cellulose, gel filtration columns and immobilized protein-G indicate that the plasma VIP binding activity is largely due to IgG antibodies. The antibodies to VIP are present in the blood of 18% of asthma patients and 30% of healthy subjects with a history of habitual muscular exercise, compared to only 2% of healthy subjects with no such history. The antibodies are highly specific for VIP, judged by their poor reaction with peptides related to VIP (i.e., GRF, PHI and secretin) . A clear di ference in the VIP binding affinity of the antibodies from asthma patients (mean K bind « 0.13 Nm "1 ) and healthy subjects (mean K^ ini « 7.7 N ' 1 ) was observed - the antibodies from the asthmatics exhibiting a 60-fold greater binding affinity. The immune IgG from asthma patients reduces the binding of VIP by lung receptors as well as the VIP-responsive synthesis of cyclic AMP in lung membranes. Thus, the antibodies can be directed against an epitope(s) that binds the receptor or maintains the receptor-binding epitope in an active conformation. These antibodies are detected by measuring their binding to porcine 125 I- IP. Human and porcine VTP are structurally identical (10). Thus, the porcine VIP- reactive antibodies found in asthma patients are autoantibodies. It had been observed that diabetics positive for plasma VIP-antibodies had been treated with insulin contaminated with VIP, suggesting that the formation of antibodies was related to the VIP contaminant (11) . The antigenic stimulus leading to formation of these autoantibodies cannot be identified with certainty. Candidate stimuli include exposure to viral determinants similar in sequence to VIP[e.g., Peptide-T, an epitope found on the human immunodeficiency virus (12)] and dietary ingestion of avian, fish and turtle VIP known to be structurally different from human VIP (13, 14). Muscular exercise, which results in increased plasma VIP immunoreactivity (15, 16), could also be a potential stimulus for VIP autoantibody formation. Indeed, asthma and muscular exercise appear to be associated with an increased incidence of autoantibodies directed against VIP. Irrespective of the type of antigenic stimulation leading to VIP-autoantibody formation, these antibodies may produce important biologic changes. The range of K β values observed for the autoantibodies of asthma patients is similar to that reported for VIP receptors present in the lung and other tissues (17, 18), and these antibodies neutralize VIP receptor binding. It is possible that VIP-autoantibodies found in asthmatics neutralize the effect of VIP in the airways. It has been discovered that these VIP- autoantibodies catalyze the hydrolysis of VIP between amino acid residues 16 and 17, i.e. between glutamine (Gin 16 ) and methionine (Met 17 ) . These are described in U.S. Application Ser. No. 343,081, filed April 25, 1989, the disclosure of which is incorporated herein by reference. Thus, specific inhibitors of catalytic autoantibodies, e.g., an inhibitor of the autoantibody which catalyzes the cleavage of VIP, would provide an important therapeutic advance for the treatment of catalytic autoantibody autoimmune disease, in particular asthma and similar respiratory diseases. More generally, inhibitors of catalytic antibodies would provide the art with the means to tailor and control the catalytic activity of such antibodies, regardless of how they are used. OBJECTS OF THE INVENTION It is a general object of the invention to provide inhibitors of catalytic antibodies. It is another object of the invention to provide inhibitors of catalytic autoantibodies. It is another object of the invention to provide a method for inhibiting a catalytic antibody or autoantibody from catalyzing a chemical reaction of a substrate. It is a further object of the invention to provide a method for treating an autoimmune disease in an animal wherein an autoantibody, which catalyzes a chemical reaction of a substrate in the animal, contributes to or is responsible for the pathophysiology of the autoimmune disease as a result of the reaction being catalyzed, by administering to the animal an inhibitor of the autoantibody. It is another object of the invention to provide a method of treating asthma and bronchitis by administering to an animal afflicted with these diseases a vasointestinal peptide (VIP) homolog which is an inhibitor of a catalytic anti-VIP autoantibody. It is still another object of the invention to provide a naturally occurring inhibitor which can be separated from naturally occurring catalytic autoantibodies. These and other objects, features, and advantages of the invention will become readily apparent from the ensuing description, and the novel features will be particularly pointed out in the appended claims. SUMMARY OF THE INVENTION The invention is broadly directed to inhibitors of catalytic antibodies and methods of making and using the inhibitors. Thus, in one aspect the invention is directed to an inhibitor which inhibits an antibody from catalyzing a chemical reaction of a substrate, the inhibitor comprising (a) a fragment of the substrate, (b) an analog of a fragment of the substrate or (c) an analog of the substrate, provided that the inhibitor was not used to elicit the catalytic antibody. In another aspect, the invention is directed to an inhibitor which inhibits an autoantibody from catalyzing a chemical reaction of a substrate. In still another aspect, the invention is directed to an inhibitor which inhibits a first antibody from catalyzing a chemical reaction of a substrate, the inhibitor comprising a second antibody which is antiidiotypic to the first antibody. Another aspect of the invention is directed to an inhibitor capable of inhibiting anti-VIP catalytic autoantibody from catalyzing the cleavage of the Gln 16 - Met 17 peptide bond in VIP which comprises VIP[22-28], The invention also concerns methods for preparing inhibitors of catalytic antibodies. Thus, in one embodiment, the invention is directed to a method for preparing an inhibitor which inhibits an antibody from catalyzing a chemical reaction of a substrate but which is not itself an antigen capable of eliciting the antibody. The method comprises the steps of synthesizing one or more fragments of the substrate; or synthesizing one or more analogs of one or more fragments of the substrate; or synthesizing one or more analogs of the substrate; and screening the fragment(s) or analog(s) synthesized in steps (a)-(c) to identify a fragment(s) or analog(s) which inhibits the antibody. In another embodiment, the invention is a method for preparing an inhibitor which inhibits an autoantibody from catalyzing a chemical reaction of a substrate. The method comprises the steps of collecting serum from an animal having the autoantibody; separating the gamma globulin fraction from the serum; separating from the gamma globulin fraction molecules which bind to the gamma globulin; and screening the molecules to identify a molecule(s) which is capable of inhibiting the autoantibody. In still another embodiment, the invention is a method for preparing an inhibitor which inhibits an autoantibody from catalyzing the cleavage or formation of a bond contained in a substrate. The method comprises the steps of synthesizing one or more analogs or one or more fragments of the substrate and screening the analog(s) or fragment(s)'to identify an analog(s) or fragment(s) which inhibits the autoantibody. Another embodiment of the invention is directed to a method for preparing an inhibitor which inhibits a first antibody from catalyzing a chemical reaction of a substrate. The method comprises the steps of generating a plurality of antibodies to the first antibody and screening the plurality of antibodies so generated to identify a second antibody which is capable of binding to and thereby inhibiting the first antibody, the second antibody being antiidiotypic to the first antibody. The invention also concerns inhibitors having been prepared by the methods described above. Accordingly, in one embodiment, the invention is directed to an inhibitor which inhibits an antibody from catalyzing a chemical reaction of a substrate, the inhibitor having been prepared by a process comprising the steps of synthesizing one or more fragments of the substrate; or synthesizing one or more analogs of one or more fragments of the substrate; or synthesizing one or more analogs of said substrate; and screening said fragment(s) or analog(s) synthesized in steps (a)-(c) to identify a fragment(s) or analog(s) which inhibits said antibody, provided that said inhibitor is not an antigen capable of eliciting said catalytic antibody. In another embodiment, the invention is directed to an inhibitor which inhibits an autoantibody from catalyzing a chemical reaction of a substrate, the inhibitor having been prepared by a process comprising the steps of collecting serum from an animal having the autoantibody; separating the gamma globulin fraction from the serum; separating from the gamma globulin fraction molecules which bind to the gamma globulin; and screening the molecules to identify a molecule(s) which is capable of inhibiting the autoantibody. In another aspect, the invention is directed to an inhibitor which inhibits anti-VIP catalytic autoantibody from catalyzing the cleavage of the Gin 16 - Met 17 peptide bond in VIP, the inhibitor having been prepared by a process comprising the steps of collecting serum from an animal having anti-VIP catalytic autoantibody, separating the gamma globulin fraction from the serum; separating from the gamma globulin fraction molecules which bind to the gamma globulin; and screening the molecules to identify a molecule(s) which is capable of binding to and thereby inhibiting the anti-VIP catalytic autoantibody from catalyzing the rate of cleavage of the Gin 16 - Met 17 peptide bond in VIP. Another embodiment of the invention is directed to an inhibitor which inhibits an autoantibody from catalyzing a chemical reaction of a substrate, the inhibitor having been prepared by a process comprising the steps of ε. thesizing one or more analogs or one or more fragments of the substrate and screening the analog(s) or fragment(ε) to identify an analog(s) or a fragment(ε) which inhibits the autoantibody. The invention is also directed to an inhibitor which inhibits a first antibody from catalyzing a chemical reaction of a substrate, the inhibitor comprising a second antibody which is antiidiotypic to the first antibody, the second antibody having been prepared by a process comprising the stepε of generating a plurality of antibodies to the firεt antibody and screening the plurality to identify a second antibody which is capable of binding to and thereby inhibiting the first antibody. The invention also concerns methods for using inhibitors to inhibit antibodies and/or autoantibodies from catalyzing a chemical reaction of a substrate. Thus, the invention is directed to a method for inhibiting an antibody from catalyzing a chemical reaction of a substrate comprising contacting the antibody with an effective amount of inhibitor under conditions suitable for the inhibition to take place, the inhibitor having been prepared by a process comprising the steps of: (a) synthesizing one or more fragments of the substrate; or (b) synthesizing one or more analogs of one or more fragments of the substrate; or (c) synthesizing one or more analogs of said substrate; and (d) screening the fragment(s) or analog(s) synthesized in steps (a)-(c) to identify a fragment(s) or analog(s) which inhibits the antibody, provided that the inhibitor is not an antigen capable of eliciting the catalytic antibody. In another embodiment, the invention is directed to a method for inhibiting an autoantibody from catalyzing a chemical reaction of a substrate comprising contacting the autoantibody with an effective amount of an inhibitor under conditions suitable for the inhibition to take place, the inhibitor having been prepared by a process comprising the steps of: (a) collecting serum from an animal having the autoantibody; (b) separating the gamma globulin fraction from the serum; (c) separating from the gamma globulin fraction molecules which bind to the gamma globulin; and (d) screening the molecules to identify a molecule.(s) which is capable of inhibiting the autoantibody. Another embodiment of the invention is directed to a method for inhibiting an autoantibody from catalyzing a chemical reaction of a substrate comprising contacting the autoantibody with an effective amount of an inhibitor under conditions suitable for the inhibition to take place, the autoantibody having been prepared by a process comprising the steps of: (a) synthesizing one or more analog,; or one or more fragments of the substrate; and (b) screening the analog(ε) or fragmen (ε) to identify an analog(s) or a fragment(ε) which inhibitε the autoantibody. In still another embodiment, the invention is directed to a method for inhibiting a first antibody from catalyzing a chemical reaction of a substrate comprising contacting the first antibody with an effective amount of a second antibody under conditions suitable for the inhibition to take place, the second antibody being antiidiotypic to the first antibody, the second antibody having been prepared by a process comprising the steps of: (a) generating a plurality of antibodies to the first antibody; and (b) screening said plurality to identify the second antibody which is capable of binding to and thereby inhibiting the first antibody. The invention also concerns methodε for uεing inhibitors of autoantibodies to treat autoimmune disease. Thus, in one embodiment, the invention is directed to a method for treating autoimmune disease in an animal wherein an autoantibody, which catalyzes a chemical reaction of a substrate in the animal, contributes to or is reεponεible for the pathophysiology of the autoimmune disease as a result of the reaction being catalyzed. The methods comprises the step of administering to the animal or to a fluid of the animal an inhibitor which inhibits the autoantibody from catalyzing the chemical reaction. In another embodiment, the invention is directed to a method for treating autoimmune disease in an animal wherein an autoantibody, which catalyzes a chemical reaction of a substrate in the animal, contributes to or is responsible for the pathophysiology of the autoimmune disease as a result of the reaction being catalyzed. The method comprises the steps of synthesizing one or more fragments of the substrate; or synthesizing one or more analogs of one or more fragments of the substrate; or synthesizing one or more analogs of said substrate; or screening said fragment(β) or analog(s) synthesized in steps (a)-(c) to identify a fragment(s) or analog(s) which inhibitε said autoantibody; and administering said inhibitor to an animal afflicted with said autoimmune disease or to a fluid of said animal. Another embodiment of the invention is directed to a method for treating autoimmune disease in an animal wherein an autoantibody, which catalyzes a chemical reaction of a substrate in the animal, cc. -ributes to or is responsible for the pathophysiology of the autoimmune disease as a result of the reaction being catalyzed. The method comprises the steps of collecting serum from an animal having said autoantibody; separating the gamma globulin fraction from said serum; separating from the gamma globulin fraction molecules which bind to the gamma globulin; screening the molecules to identify a molecule(s) which is capable of binding to and thereby inhibiting said autoantibody from catalyzing the chemical reaction of the substrate; and administering a molecule(s) identified in step (d) to an animal afflicted with said autoimmune disease or to a fluid of said animal. In still another embodiment, the invention is directed to a method for treating autoimmune disease in an animal wherein an autoantibody, which catalyzes a chemical reaction of a substrate in the animal, contributes to or is responsible for the pathophysiology of the autoimmune disease as a result of the reaction being catalyzed. The method comprises administering to the animal or to a fluid of the animal an inhibitor which inhibits the autoantibody from catalyzing the chemical reaction, the inhibitor having been prepared by a procesε comprising the steps of synthesizing one or more fragments of the substrate; or synthesizing one or more analogs of one or more fragments of the substrate; or synthesizing one or more analogs of the substrate; and screening said fragment(s) or analog(s) synthesized in steps (a)-(c) to identify a fragment(s) or an analog(s) which inhibitε said autoantibody. Another embodiment of the invention is directed to a method for treating autoimmune disease in an animal wherein an autoantibody, which catalyzes a chemical reaction of a substrate in the animal, contributes to or is responsible for the pathophysiology of the autoimmune a..*ease as a result of the reaction being catalyze The method comprises the step of administering to an animal afflicted with the autoimmune disease or to a fluid of the animal an inhibitor which inhibits the autoantibody from catalyzing the chemical reaction, the inhibitor having been prepared by a process comprising the steps of collecting serum from an animal having said autoantibody; separating the gamma globulin fraction from said serum; separating from the gamma globulin fraction molecules which bind to the gamma globulin; and screening the molecules to identify a molecule(s) which is capable of binding to and thereby inhibiting said autoantibody from catalyzing the chemical reaction of the substrate. Another aspect of the invention is directed to a pharmaceutical composition for treating autoimmune disease in an animal wherein an autoantibody, which catalyzes a chemical reaction of a substrate in the animal, contributes to or is responsible for the pathophyεiology of the autoimmune diεeaεe aε a reεult of the reaction being catalyzed. The composition comprises an inhibitor which inhibitε the autoantibody from catalyzing the chemical reaction and a pharmaceutically suitable carrier. In still another aspect, the invention is directed to a pharmaceutical composition for treating asthma which compriseε an inhibitor which inhibitε anti- VIP catalytic autoantibody from catalyzing the cleavage of the Gin 16 - Met 17 peptide bond in VIP, said inhibitor having been prepared by a proceεε comprising the steps of collecting serum from an animal having anti-VIP catalytic autoantibody; separating the gamma globulin fraction from the serum; separating from the gamma globulin fraction molecules which bind to the gamma globulin; and screening the molecules to identify a molecule(s) which is capable of binding to and thereby inhibiting the autoantibody from catalyzing the rate of cleavage of the Gin 16 - Met 17 peptide br; -i in VIP, and a pharmaceutically suitable carrier. Yet another aspect of the invention iε directed to a pharmaceutical composition for treating asthma which comprises VlP[22-28] and a pharmaceutically suitable carrier therefor. BRIEF DESCRIPTION OF THE DRAWINGS The invention will be understood more clearly and fully from the following detailed description, when read with reference to the accompanying figures, in which: Fig. 1 shows the separation of mono ( 125 I, Tyr 10 )-VIP and di( 125 I, Tyr 10 , Tyr 22 )-VIP by reverse phase HPLC; Fig. 2 shows reduced precipitation of mono( 125 I, Tyr 10 )-VIP treated with 42.5 ug of the anti-VIP antibody fraction (A) as compared to an equivalent concentration of a nonimmune antibody fraction (•); Fig. 3 shows mono ( 12S I, Tyr 10 )-VIP hydrolysis by IgG: saturation by increasing concentrations of VIP; Fig. 4 shows a Scatchard plot (A) and Hill plot (B) of VIP binding by the IgG; Fig. 5 shows the reverse phase HPLC of mono ( 125 I, Tyr 10 )-VIP treated with intact IgG or IgG boiled for ten minuteε; Figε. 6, 7 and 8 show reverse phase HPLC purification of VIP fragments produced by treatment with the anti-VIP antibody fraction; Figs. 7 and 8 show the amino acid sequences of the VIP fragments determined by the Edman degradation method; Fig. 9 shows a partial positive ion fast atom bombardment-mass spectrum (m/z 1200-1500) of the VIP fragment (2) purifi .1 in Fig. 8; Fig. 10 is a plot of % VIP degraded versuε concentration of IgG which (i) received no ultrafiltration (•) and (ii) received ultrafiltration ( ); Fig. 11 shows ten synthetic VIP homologs (frag entε) wherein (-—) denoteε the bond cleaved (scissile bond) by anti-VIP catalytic autoantibody; Fig. 12 shows saturable (Tyr 10 - 125 I)-VIP binding by the autoantibody fraction (100 μg purified IgG) : Competitive inhibition by VIP(o), VIP[15-28](■) , VIP[22- 28](«), and VIP[18-24] (A); Fig. 13 shows catalytic hydrolysiε of VIP[1-28] by the autoantibody (50 μg IgG) : Inhibition by 100 μM VIP[22-28], (Tyr 10 - 125 I)-VIP (32 pM) mixed with increaεing VIP concentrationε waε treated with the IgG in the absence (•) and presence (A) of VIP[22-28]; Fig. 14 is a Scatchard plot of VIP binding by the IgG; Fig. 15 shows an affinity chromatograph of human IgG on a VIP-Sepheroεe column, with the arrow indicating the shift to a low pH buffer and the inset shows hydrolysis of (Tyr 10 - 125 I) VIP as a function of concentration of acid eluted antibody concentration; Fig. 16 shows reducing SDS-polyacrylamide gel electrophoresiε of affinity-fractionated VIP autoantibodies stained with anti L-chain antibody (lane 1), anti-H-chain antibody (lane 2) and silver (lane 3); Fig. 17 shows reverse phase HPLC of (Tyr 10 - 125 I) VIP treated with unfractionated IgG (upper panel) , affinity-fractionated VIP antibodies (middle panel) , and assay diluent (lower panel) , with arrowε showing the retention time of synthetic ( 125 I) (VIP[1-16]) and unhydrolyzed (Tyr 10 - 25 I) VIP; and Fig. 18 showε Lineweaver-Burke plotε of VIP hydrolysis by affinity-frac " onated VIP antibodies (upper panel) and unfractionated IgG (lower panel) . DETAILED DESCRIPTION OF THE INVENTION The invention is broadly directed to inhibitors which are capable of inhibiting catalytic antibodies from catalyzing a chemical reaction. "Catalytic antibody" as used herein is a substance which is capable of changing the rate of a chemical reaction, all other conditions (e.g., temperature, reactant/substrate concentration, etc.) being the same and which does not enter into the chemical reaction and, therefore, is not consumed in the reaction. It is also a substance which exhibits the capability of converting multiple moles of reactant substrate per mole of catalytic antibody; and which, from a mechaniεtic viewpoint, binds the reactant/βubstrate, effectε the accelerated conversion of the reactant/substrate to the product and then releaseε the product; and which changes the rate of the chemical reaction without shifting the position of the equilibrium. While the aforementioned definitions are characteristics of ideal catalysts, in practice, even the best of catalysts become poisoned or deactivated by contamination in the reaction system or as a result of chemical or physical destruction during the reaction procesε. For reasons well-known in the art, the true operation of a catalyεt may be obscured by componentε of the reaction system or by the condition of the reaction environment. The art has adopted certain working definitions to express catalytic activity. These expressions are [1] k eat , or "turnover" and [2] k cat /k uncat , the "rate enhancement factor". Turnover indicates the number of molecules of reactant/substrate which can be converted to product per mole of catalytic antibody per unit time. For example, if a molecule exhibitε a turnover of 10 3 of substrate er minute and the molecule. laintains its catalytic activity for 24 hours at room temperature and at its optimal pH, each molecule of catalyst would then make a total of 1.4 x 10 converεionε, indicating itε catalytic behavior. Thiε total conversion is to be distinguished from the total conversion in a stoichiometric reaction, which will never exceed 1.0, no matter how long the reaction is carried out. The rate enhancement factor iε a dimensionless number which expresses the rate of reaction in the presence of catalyst to the rate of reaction in the absence of catalyst, all other reaction conditions being equal. In accordance with the invention, an antibody can comprise purified immunoglobulins (IgG, IgM, IgA, IgD or IgE) or antibody fragments, such as, for example. Fab, F(ab') 2 , Fv, etc., of immunoglobulins. Catalytic antibodies include two major categories. The first category includes catalytic antibodies which have been rationally designed, i.e., antibodies elicited with an antigen introduced by specific immunization against a target antigen or substrate. Such catalytic antibodies, processes for their preparation and their use are described in U.S. Patent 4,888,281, issued December 19, 1989, U.S. Patent 4,792,446, isεued December 20, 1988 and U.S. Application Serial No. 064,239, filed June 19, 1987, all of the disclosureε of which are incorporated herein by reference. The other category of catalytic antibodies includeε naturally occurring antibodieε which are produced by an animal's immune system to the animal's own cellular component (self-antigen) , as opposed to the first category of catalytic antibodieε previouεly described. These "autoantibodies" are described in U.S. Application Serial No. 343,081, filed April 25, 1989, the disclosure of which is incorporated herein by reference. An inhibitor in accordance with the invention prevents a catalytic antibody from catalyzing a chemical reaction of a substrate. The inhibitor binds * :o the catalytic antibody, thereby preventing the catalytic antibody from binding to the subεtrate and catalyzing the reaction of the substrate. The term "chemical reaction" refers to a reaction wherein at least one reactant is converted to at least one product. Such chemical reactions include chemical reactions which can be catalyzed by enzymes such as, for example, oxoreductaεeε, tranεferaεeε, hydrolaεeε, lyases, isomerases and ligases, as well aε chemical reactions for which no catalytic enzymes are known such aε, for example, oxidationε, reductions, additions, condensations, eliminations, substitutionε, cleavages and rearrangements. In one embodiment of the invention, the chemical reaction is the cleavage of a peptide bond. Peptide bond as used herein refers to an amide bond linking two adjacent amino acid residues and is generically represented by the following formula wherein the peptide bond is shown within the box: ♦ H 3 Ϊ C - 0 ' An amino acid consiεtε of a carbon atom to which iε bonded an amino group, a carboxyl group, a hydrogen atom and a distinctive group referred to aε a "side chain" (R, and R j in the formula above) . Amino acid as used herein includes the twenty naturally occurring amino acidε which comprise the building blocks of proteinε. It iε understood by those skilled in the art that when either of the adjacent amino acids iε proline, the reεpective side chains R, or R j are bonded to the adjacent nitrogen atoms to form the characteristic 5-membered proline ring. The term "substrate" is synonymous with the reactant in the chemical reaction and can be any of a number of molecules and biomoleculeε including but not limited to peptideε, proteinε, phospholipids, carbohydrateε (e.g., glycogen, glucoεe, etc.) and drugs (including abuεed substanceε and drugs from exogenous sources) . In one embodiment, the substrate contains a peptide bond or bonds to be cleaved and can be any proteinaceouε molecule, such as, for example, a regulatory protein or a structural protein including but not limited to peptide hormones (e.g., insulin, growth hormone, secretin, etc.), peptide neurotransmitters, neuromodulators and neurohumoral factors (e.g., VIP, endorphins, enkephlins, bradykininε, εubstance P., etc.), tumor proteins (e.g., oncogene products, carcinoembryonic antigens,, etc.), bacterial proteins and viral proteins (e.g., human immunodeficiency viral (HIV) gp 120 influenza glycoproteins, etc.). In another embodiment, the substrate can be a self-antigen, i.e., any antigen which the body makes using its own genetic code. Thuε, self-antigens are distinguished from foreign antigens (e.g., bacterial, viral antigens). The term "animal" aε used herein refers to any organism with an immune system and includes mammalian and non-mammalian animals. In accordance with one embodiment of the invention, an inhibitor can comprise a fragment of the substrate, an analog of a fragment of the substrate or an analog of the substrate provided that, in the case of catalytic antibodies elicited by specific immunization within an antigen, the inhibitor iε not an antigen capable of eliciting the catalytic antibody. The term "fragment of the substrate" refers to a molecule which represents some portion of the substrate. For example, if the substrate is a peptide, the inhibitor can be a fragment of the peptide, e.g., one or more homologous peptides having amino acid residues which are identical to amino acid residues in one or more portions of the pept: 2 substrate. The term "analog" is used in its broadest sense and includes isomerε, homologε or any molecule which sufficiently resembles the substrate in terms of chemical structure such that an antibody raiεed against the analog may participate in an immunological reaction with the substrate but will not necessarily catalyze a reaction of the analog. For example, an analog of the substrate can be a molecule which is structurally similar to the subεtrate but differs from the substrate by one or more elements of the same valance and group of the periodic table as the element or elements replaced in the subεtrate, e.g., an analog of the transition state of the reaction to be catalyzed. An analog of the substrate in accordance with the invention can also be an optical antipode of the substrate. For example, if the substrate is a D-amino acid, an inhibitor in accordance with the invention would be the L-optical antipode. In the case of an autoantibody where the substrate is a self-antigen, an inhibitor of the autoantibody can be an analog of the self-antigen, a small peptide containing an epitope of the self-antigen at which epitope the chemical reaction does or does not take place, an analog of a rmall peptide containing the epitope, or a small peptide containing an analog of the epitope. The above-described inhibitors can be synthesized by a variety of chemical and immunological biosynthetic methodologies well-known in the art (19) . Another embodiment of the invention is directed to an inhibitor comprising an antibody which is antiidiotypic to the antibody to be inhibited. An antibody that iε "antiidiotypic" refers to an antibody that bindε to a second antibody on the variable region of the second antibody. Such an inhibitor iε prepared by generating a plurality of antibodieε to the catalytic antibody and screening the plurality to identify an antiidiotypic antibody which is capable of binding to and thereby inhib^iing the catalytic antibody. Methods for the generation of the plurality of antibodies and screening assayε for binding and inhibition are well- known in the art. In a preferred embodiment, an animal is immunized with the catalytic antibody to generate antibody-producing lymphocytes in the animal which are then removed from the animal and fused with myeloma cells to produce a plurality of hybridoma cells each in turn producing monoclonal antibodieε. The monoclonal antibodieε can then be εcreened for binding to and inhibition of the target catalytic antibody by methods well-known in the art (6) . The hydrolytic activity of anti-VIP catalytic autoantibody iε latent because of the presence of a tightly bound, relatively εmall sized inhibitor. This latency was based on the discovery that little or no VIP hydrolytic activity waε present in the IgG fraction of serum isolated from individuals having the anti-VIP catalytic autoantibody when the IgG waε tested for hydrolytic activity directly after purification on immobilized protein G (6) . However, VIP hydrolytic activity was observed when the IgG was subjected to any of the following treatments: (a) extensive dialysis; (b) two cycles of ultrafiltration; (c) prolonged washing of the IgG at neutral pH when bound on protein G-Sepharose; or (d) affinity chromatography on a VIP-Sepharose column. The binding of an antigen (or an inhibitor) to an antibody is an equilibrium reaction as follows: 'bind Antibody + λntigen(Inlιibitor) * > x nnbmd Antibody:Antigen(Inhibitor) Treatments (a)-(d) remove unbound inhibitor forcing the equilibrium to the left (k^^) and facilitating further removal of inhibitor, c.:d thereby leaving behind hydrolytically active antibody. Thus, in still another embodiment, the invention is directed to naturally occurring inhibitors of catalytic autoantibodies. The inhibitor is prepared by collecting serum from an animal having the target catalytic autoantibody, separating the gamma globulin fraction from the serum, separating from the gamma globulin fraction molecules which bind to the gamma globulin and screening the molecules so separated to identify a molecule which is capable of inhibiting the catalytic activity of the target autoantibody. These molecules include metal ions, antibodies, antibody fragments, etc. and are typically low molecular weight molecule's ranging in weight from 1,000 to 15,000 Daltons. In one embodiment, the molecules are separated from the gamma globulin fraction by ultrafiltration or by dialysis. The term "ultrafiltration" aε used herein refers to a process for separating proteins from small molecules whereby pressure or centrifugal force is uεed to filter a liquid medium and small solute molecules through a semipermeable membrane having pores with an average cut-off molecular weight ranging from 1000 to 10,000 Daltons. Thus, for example, ultra litering an immunoglobulin with a molecular weight of 150,000 Daltons on a membrane with pores having an average cut-off molecular weight of 10,000 Daltons will cause molecules with molecular weights smaller than 10,000 Daltons to pasε through the membrane into the ultrafiltrate while the immunoglobulin remains on the membrane. Accordingly, potential inhibitors will be found in the ultrafiltrate. The ultrafiltrate is then partially purified and fractions thereof are then screened for binding and inhibitory activity. Fractions showing inhibitory activity are subjected to further separation procedures in order to yield the pure inhibitor. Once isolated, the pure inhibitor is subjected to aino acid analysis and peptide sequencing and/or to other types of chemical analysis in order to identify the chemical structure. The term "dialysis" as used herein refers to a procesε for separating globular proteins in solution from low-molecular weight solutes which utilizes a semipermeable membrane to retain protein molecules and allow small solute molecules and water to paεε through. Dialysiε membranes with molecular weight cut-offs ranging from 12,000-15,000 Daltonε are advantageously used. Potential inhibitors in the dialyεate are then screened for inhibitory activity and purified in a manner analogous to that described above with reference to ultrafiltration. In another embodiment, molecules which bind to the gamma globulin are separated by washing after immobilization of the IgG on a non-specific protein support or by affinity chromatography on a protein support which iε specific for the particular antibody for which an inhibitor is being sought. An example of a non¬ specific protein support is Protein G-Sepharose. Protein G-Sepharose will bind the F e region of all antibodieε. Thus, in the case of anti-VIP catalytic autoantibody, Protein G-Sepharose will bind F e region of all antibodies in the sample as well as the F c region of the anti-VIP catalytic autoantibody. Once the IgG in the sample iε immobilized, it iε then washed with buffer to remove putative inhibitors. The putative inhibitors are then screened for inhibitory activity and purified in a manner analogous to that described above. The column is then washed with an acidic solution to release the free, activated IgG. Affinity chromatography involves the use of a protein support which is specific only for the particular antibody for which an inhibitor is being sought because it will bind only to the variable region (i.e., antigen binding region) of the antibody. Affini*— chromatography forces the antibody-inhibitor binding equilibrium in the direction of dissociation of the inhibitor because there is a competition between the inhibitor and the specific protein for the binding site on the antibody. Thus, affinity chromatography provides for the isolation of active site-directed inhibitors and, therefore, requires less washing to remove putative inhibitors than is required with the non-specific protein support described above. The putative inhibitors are then screened for inhibitor activity and purified in a manner analogous to that described above. The column iε then washed with an acidic solution to release the free, activated IgG. In the case of anti-VIP catalytic autoantibody, a VIP- Sepharose column is advantageously used. The inhibitors of the invention can then be used to inhibit a catalytic antibody from catalyzing the rate of a chemical reaction of a substrate. The catalytic antibody is contacted with an effective amount of the inhibitor under conditions suitable for the inhibition to take place. Suitable conditions for inhibition are any conditions which allow binding of the inhibitor to the target catalytic antibody. Typically these conditions are physiologic conditions, i.e., conditions found in vivo (e.g., in the blood). As noted above, it iε well-known that certain autoimmune diseases are associated with autoantibodies directed against hormones and cell surface antigens. In autoimmune diseases where an autoantibody contributes to or is responsible for the pathophysiology of the disease as a result of catalyzing a reaction of a substrate, a methodology for treating autoimmune disease presents itself based on the use of an inhibitor, in accordance with the invention, of that autoantibody. Thus, another embodiment of the invention is directed to a method for treating autoimmune disease in an animal wherein an -t-Loantibody, which catalyzes a chemical reaction of a substrate in the animal, contributes to or is responsible for the pathophysiology of said autoimmune disease as a result of the reaction being catalyzed. The method comprises administering to an animal afflicted with the autoimmune disease or to a fluid of such an animal an inhibitor in accordance with the invention which inhibits the autoantibody from catalyzing the chemical reaction. In a preferred embodiment, the inhibitor is administered directly to the animal as a pharmaceutical composition comprising the inhibitor and a suitable pharmaceutical carrier, either orally or by injection (I.V. or I.M.). In another preferred embodiment, the inhibitor is administered to the animal extracorporeally; i.e., a fluid of the animal, e.g., blood, is passed from the animal's body through a matrix which is impregnated with an inhibitor according to the invention. The autoantibody aεsociated with the pathophysiology of the autoimmune disease is removed from the fluid as a result of binding between the inhibitor and the autoantibody, and the fluid is then returned to the body of the animal. Autoimmune diseases which can be treated in accordance with the invention include asthma, bronchitis, diabetes and impotence. DESCRIPTION OF CERTAIN PREFERRED EMBODIMENTS Certain preferred embodiments of the invention are directed to inhibitorε of an autoantibody ("anti-VIP catalytic autoantibody") which catalytically cleave the peptide bond between glutamine and methionine ("Gln 16 -Met 17 ") in VIP. In one embodiment, inhibitors are a family of peptide homologs of VIP which bind to the anti-VIP catalytic autoantibody without themselves undergoing catalytic cleavage. Thus, ten synthetic peptide homologs (fragments of VIP) (Fig. 11) , corresponding to linear subsequences of VIP, v—e screened for their reactivity with (Tyr 10* 125 I)VIP binding autoantibody. IgG purified from the plasma of a human subject was the source of the antibody. The binding screens were performed using: (1) IgG which had not been dialyzed to remove the putative inhibitor of hydrolysis; (2) a temperature of 4°C; or (3) buffer (7.5 M sodium phosphate, pH 7.4, 0.64% sodium chloride, 0.5% bovine serum albumin, 25 mM EDTA, 0.005% bacitracin, 0.005% protamine sulfate, 0.073% sodium azide and 0.025% Tween-20) , i.e., experimental conditions non-permissive for (Tyr 10'125 I)VIP hydrolysiε. The N-terminal fragment VIP[1-16] at 500 μM failed to inhibit binding of (Tyr 10' 25 I)VIP. The C-terminal fragment VIP[15-28], in contrast, inhibited the binding with potency (K, 1.25 nM) close to that of the full length peptide, VIP[1-28] (K p 0.3nM) (Fig. 12). Of the seven shorter peptides teεted initially at a concentration of 500 μM each, only VIP[22- 28] and VIP[l8-24] inhibited (Tyr 10 " 125 I)-VlP binding. The K. for VIP[22-28] was 242 μM. VIP[22-28] showed approximately 8-fold greater potency than VIP[18-24]. Therefore, the reactivity of the latter peptide is believed to be due to the shared sequence VIP[22-24]. The apparent binding energy for the peptides were, in kcal/ ole, VIP[l-28], 12.1; VIP[ 5-28], 11.3; and, VIP[22-28], 4.6. The binding energy of residues 22-28 is substantial, although it is only 38% of that for the full length peptide. Because VIP[22-28] bound the autoantibody the strongest in comparison to the other homologs, it was screened for catalytic inhibitory activity by measuring its effect on catalysiε by the autoantibody. Hydrolyεiε of increaεing concentrationε of VIP in the absence and presence of VIP[22-28] was compared. The plot of the reciprocal rate of VIP hydrolysis versus the reciprocal concentration of VIP (Fig. 13) was linear, indicating conformity with Michaelis-Menten kinetics. K, and k eat values for the VIP .<l«avage in the absence of VIP[22-28] were 115 ± 14nM and 6.5 ± 0.3 min" 1 , respectively. In the presence of 100 μM VIP[22-28], the apparent K., was increaεed (159 ± 4nM) and k cat waε unchanged (6.9 ± 0.2 min 1 ), suggesting competitive inhibition of VIP hydrolysis. K j for VIP[22-28] calculated from these data was 260 μM. VIP[22-28] treated with the IgG did not itself undergo cleavage. It was assumed that the binding and hydrolysis of VIP iε mediated by the same autoantibody present in the IgG because: (i) Scatchard analysiε of VIP binding suggested that the IgG contains a single class of VIP binding antibody (6) ; (ii) specific antibody purified from the IgG by binding to VIP coupled to a solid support was found to hydrolyze (Tyr 10* 25 I)VIP at the same peptide bond (Gin 16 - Met 17 ) as the starting IgG; and (iii) the subsequence VIP[22-28] not only inhibited the binding of full length VIP by the IgG, but also its hydrolysis. The reactivity of VIP[22-28] with the catalytic autoantibody appears to be sequence-specific because: (i) inhibition of (Tyr 10*125 I)VIP binding and hydrolyεiε by the VIP[22-28] was competitive in nature; (ii) the inhibition was observed despite presence of an excess (>300-fold, by weight) of an unrelated protein (BSA) ; and (iii) 400 μM V P[l-7], a non-binding fragment, did not inhibit VIP hydrolysis. This assumption was confirmed by affinity chromatography of the IgG on VIP-Sepharose. VIP[22-28] does not contain the βcissile peptide bond (Gin 16 - Met 17 ) , but it binds the catalytic autoantibody and inhibits antibody-catalyzed VIP hydrolysis. Thus, amino acid residues distant from the site of the chemical reaction are believed to be important in substrate recognition and binding by the antibody. Antibody binding pockets appeared to be relatively large, capable of contacting aε many aε 16 amino acidε of antigen (20) . VIP[22-28] bound the catalytic autoantibody with- ignif.icant energy (4.5 kcal/mol) , but this energy is only 41% that of VIP[15- 28]. These data suggest that VIP[15-28] iε the epitope recognized by the catalytic antibody, and VIP[22-28] iε a •subepitope' that contributes some, but not all antibody binding interactions. This conclusion iε consistent with previous findings that small fragments of protein antigens usually show low affinity binding to antibodies raised against the parent proteins (21) . The exact contribution of residues 15-21 of VIP in binding to the catalytic autoantibody is uncertain. Linear VIP fragments consisting of residues 15-21, 11-17 and 13-20 did not interact significantly with the catalytic autoantibody in the binding assays, but the residueε at the scisβile bond (Gin 16 - Met 17 ) must contact the catalytic group(ε) in the antibody active site in some manner. One or more residueε in VIP[15-21] may be integral to a conformational determinant recognized by the autoantibody. On the other hand, theεe residues may contribute relatively nonspecifically to increase the binding energy of VIP[22-28], since N-terminal extension of small peptides with irrelevant amino acids or octanoyl groups is known to increase their antibody binding affinity (22). Conventional peptidases hydrolyze a broad range of proteinε with specificities dictated primarily by the type of amino acids at or in the immediate vicinity of the scissile bond (23) . In the case of relatively specific peptidases like renin (24), 3 or 4 amino acid residueε located on each side of the cleavage site can influence enzyme binding. Even in these cases, it is believed that binding of substrate subsequences devoid of the sciεεile bond has not been shown. In contrast, the catalytic autoantibody exhibits significant binding of residueε 22-28 of VIP, located 4 amino acidε distant from the scissile bond. The recognition u f a distant peptide sequence may be interpreted to reflect an extraordinary substrate specificity of this catalytic antibody, compared to conventional peptidases. There iε evidence in the case of enzymes that binding energy from interactions at residueε other than those at the scissile bond iε utilized to increase the catalytic rate (25) . It iε believed that binding at residues 22-28 of VIP facilitates catalysiε by the antibody. In another preferred embodiment of the invention, the inhibitor iε a naturally occurring compound which binds to and thereby inhibitε the catalytic activity of anti-VIP catalytic autoantibody. As stated earlier, it had been discovered that little or no VIP hydrolytic activity was present in the IgG fraction of serum iεolated from individualε having the anti-VIP catalytic autoantibody when it waε tested directly after purification on immobilized protein G (6) . However, VIP-hydrolytic activity was observed after subjecting the IgG to ultrafiltration. It has now been discovered that removal of a tightly bound naturally occurring inhibitor imparts VIP-hydrolytic activity to the autoantibody. Thuε, in accordance with the invention, the naturally occurring inhibitor of anti-VIP catalytic autoantibody iε prepared by collecting serum from an animal having the autoantibody, separating the gamma globulin fraction from the serum by methods known in the art, subjecting the gamma globulin fraction to ultrafiltration in order to separate lower molecular weight molecules from the gamma globulin fraction and then screening the lower molecular weight molecules in the ultrafiltrate for binding and inhibitory activity. Fractions of the ultrafiltrate testing positive for inhibitory activity are further purified and the chemical structure of the inhibitors are identified by methods known in the art. It has been observed that airway di. orders, in particular asthma and bronchitis, are associated with VIP autoantibodies, some of which possesε catalytic activity (9) . The disease causing potential of catalytic antibodies directed againεt self-antigens like VIP iε greater than that of antibodies that merely bind self- antigens. Thus, high affinity peptide homologs and naturally occurring inhibitors like those just described can be used to treat airway disorders, in particular asthma. The invention will be more fully described and understood with reference to the following examples which are given by way of illustration. Example 1 Preparation Of Mono< 125 I-TYR 10 l-VIP Purified porcine VIP (Bache ) was labeled with 12S iodine by the chloramine-T method (26) . The resulting mono ( 125 I-Tyr 10 )-VIP was purified on a Seppak C18 cartridge followed by reverse phaεe HPLC with a gradient of acetonitrile in trifluoroacetic acid. Two major peaks of radioactivity were obtained (Fig. 1) , corresponding to compounds that reacted with rabbit anti-VIP antiseru in radioimmunoassay. In order to obtain sufficient peptide for sequencing, VIP was iodinated with 12S I diluted with 127 I to reduce the specific activity, and purification performed as before. Analysis of the peak with retention time 25.3 min on an Applied Bioεysterns sequenator with on-line phenylthiohydantoin amino acid detection showed radioactivity mainly in cycle 10, with HPLC characteristics similar to those of monoiodotyrosine (purchaεed from Calbiochem) , indicating that this material waε mono( 125 I-Tyr 10 )-VIP. The second peak of radioactivity (retention time 27.8 min) was identified as di( 125 I-Tyr 0 ,Tyr 22 )-VIP by similar methods. The di( 125 I- Tyr 10 ,Tyr 22 )-VIP and mono( 125 I-Tyr 10 )-VIP performed nearly equivalently in a radioimmuiioassay test. Since native VIP, VIP oxidized with chloramine-T without Na 125 I(CT-VIP) and mono ( 125 I,Tyr 10 )-VIP were well separated, it was concluded that the 25 I-VIP was free of unlabeled peptide. Example 2 Demonstration Of VIP Autoantibodies In Human Subjects The antibodies were measured in plasma samples from asthma patients and healthy subjects, subdivided into high exercise (Hx) and low exerciεe (Lx) subgroups (8). Asthma waε diagnoεed on the baεiε of patient hiεtory and typical clinical indicators. The healthy Hx subjects had a history of habitual muscular exercise, and the healthy Lx subjects did not. Human blood samples were collected in a mixture of peptide hydrolase inhibitors (aprotinin, phenylmethylsulfonyl fluoride, pepstatin, ethylene diamine tetracetic acid) (9) . The immunoglobulin G (IgG) fraction from blood was prepared by sequential chromatography (7,9) on DEAE-cellulose (Whatman) and protein G-Sepharose (Pharmacia) . The IgG (4 mg/ml) was ultrafiltered on a YM-10 membrane having an average cut off molecular weight of 10,000 Daltons using an Amicon Model 8 MC apparatuε to 27 mg/ml, diluted back to 0.8 mg/ml and then subjected to a second cycle of ultrafiltration. The final concentration of IgG prepared in this manner was about 20 mg/ml. Electrophoretic analysis and staining of nitrocellulose blots with anti- human IgG conjugated to peroxidaεe did not reveal presence of non-immunoglobulin material in this preparation. The presence of VIP-antibodies waε established by measuring saturable binding of mono( 125 I- Tyr 10 )-VlP (binding inhibited by excess unlabelled VIP) in plasma samples or purified IgG. The monoiodinated form of VIP was used because it is more likely to reproduce the interactions of native VIP with the antibodieε. Bound and free VIP were separated by precipitation with poly hylene glycol or specific sheep antibodies against human IgG (9) . Plasma samples from some asthma patients and healthy subjects were observed to exhibit saturable 125 I-VIP binding activity (up to 67.5% of total 125 I-VIP) . The VIP-antibodies were found in 18% of asthma patients (N=74) , 30% of healthy Hx subjects (N=51) , 2% of healthy Lx subjects (N«44) . The mean 125 I-VIP binding values (%B/T with SEM in parentheses) in the antibody positive asthma and Hx subjects were 23.4 (5.3) and 20.4 (3.2). The lone antibody positive subject in the Lx group showed a % B/T value of 12.1%. Example ? Hvdrolvsiβ Of V P Bv Anti-VIP Autoantibodies To compare antibody mediated hydrolysis and spontaneous hydrolyεiε of the peptide VIP, mono( 125 I- Tyr 10 )-VIP waε incubated with (i) immune and (ii) nonimmune IgG for increasing lengths of time. IgG from a nonimmune human subject and a VIP antibody positive subject was prepared by chromatography on DEAE celluloεe followed by ultrafiltration aε described in Example 2. The IgG or assay diluent (final volume of 200 μl in 50 mM Tris-HCl, 100 mM glycine, 0.025% Tween-20 and 0.1% bovine serum albumin, pH 8.0) was incubated with mono ( 125 I,Tyr 10 )-VIP (approximately 30 p) for increasing lengths of time at 38°C. Bovine serum albumin and Tween- 20 were included in these incubations to prevent adsorptive loss of the mono ( 25 I,Tyr 10 )-VIP on glass and plastic surfaces. Precipitation with trichloroacetic acid (TCA) (27) was used as the initial criterion of mono( 125 I,Tyr 10 )-VIP degradation (6). Accordingly, l ml of TCA (final concentration 10% v/v) was added to the reaction mixtures which were then centrifuged at 3000 xg. The supernatants were aspirated and the radioactivity was measured in the pellets (Beckman model 5500 spectrometer) . At this TCA concentration, greater than 90% of intact mono ( 25 I,Tyr 10 )-VIP waε precipitated (i.e., found to appear in the TCA-inεoluble pellet) . Valueε for VIP hydrolysis were computed from the radioactivity observed aε countε per minute (CPM) in the TCA- precipitable fractionε as: < CPM .s.ay buffer " CPM .ntibody) x "O/C∞ buffer' Compared to 8% hydrolysiε of the mono ( 125 I,Tyr 10 )-VIP incubated with nonimmune IgG, 73% of the peptide waε hydrolyzed by treatment with immune IgG. The ability of the IgG to hydrolyze mono- ( 125 I,Tyr 10 )-VIP was not lost by precipitation with 50% saturated ammonium sulfate or ultrafiltration on a 100 kDa membrane filter. Treatment of the IgG with rabbit anti-human IgG or treatment at 100°C (10 min) prior to incubation with mono( 125 I,Tyr 10 )-VIP destroyed the hydrolytic activity of the IgG aε indicated by a reduction in the amount of radioactivity in the peak with RT of 10 min. Treatment of mono ( 125 I,Tyr 10 )-VIP with immune IgG for increaεing time periodε progressively reduced the amount of radioactivity precipitated by 10% TCA (starting radioactivity in each tube was 15,040 CPM) , as shown in Fig. 2. After incubation with immune IgG for 6h, 73% of the starting mono ( 125 I,Tyr 10 )-VIP was no longer precipitated by TCA, compared to only 8% of the mono ( 2s I,Tyr 10 )-VIP incubated with nonimmune IgG. The degradation of mono ( 125 I-Tyr 10 )-VIP waε pH dependent, with an optimum pH of 8.0-8.5. Kinetic data were obtained by incubating IgG with increaεing concentrations of unlabeled VIP mixed with a fixed concentration of mono ( 125 I,Tyr 10 )-VIP aε trace for 2 h at 38 β C. The hydrolysis waε saturable with increasing VIP concentrations and a plot of 1/velocity vs. 1/substrate concentration was linear, as shown in Fig. 3, indicating that the reaction conformed to Michaelis-Menten kinetics (data fitted to Michaelis- Menten equation using "NZFITTER (Elsevier) ) . A K, for che reaction of 37.9 nM, determined from the slope of the linear plot in Fig. 1, indicated relatively stable antibody-VIP binding. A Scatchard plot of VIP binding by the antibody, under conditions that did not lead to VIP hydrolyεiε, waε linear, aε shown in Fig. 4A. The slope for the Hill plot, shown in Fig. 4B, was close to unity (1.02). These data indicated a single antibody clasε with K d 0.4 nM and concentration 73.4 fmol/mg IgG (aεεuming antibody bivalency) . The k cat and k cat /K 1 . valueε for the hydrolyεiε, computed on the baεiε of the kinetics of hydrolyεiε and the antibody concentrationε obtained from the binding data, were 0.26 sec" 1 and 6.9 x lO^^sec " 1 . These values indicated that the anti-VIP acts catalytically to hydrolyse VIP. A turnover of 0.26 sec "1 (i.e., about 16 molecules of VIP are hydrolyzed by one molecule of antibody per minute) was calculated. This calculation was based on the total number of antibodieε which were capable of binding to VIP. However, in reality, not all antibodies capable of binding to VIP are necessarily capable of catalytic hydrolysis of VIP. Therefore, the actual turnover number iε probably greater than that calculated. XWTT. l --. _f Identification Of Peptide Fragments Resulting From Hydrolysis Of V P Catalyzed Bv Anti-VIP Autoantibodies Reverse phase HPLC of mono ( 125 I-Tyr 10 )-VIP treated with the immune IgG revealed a reduction in the amount of intact mono ( 125 I, Tyr 10 )-VIP (retention time (RT):25 min.) and the appearance of an early eluting peak of radioactivity (RT:10.0 min) that waε well separated from intact mono ( 125 I-Tyr 10 )-VIP and free 125 I (RT:65-7.0 min) (Fig. 5) . Heat treatment «-<f the IgG prior to incubation with mono(Tyr 10 , 125 I)-VIP resulted in a reduction in the amount of radioactivity in the peak with RT 10 min. When mono ( 125 I, Tyr 10 )-VIP was incubated in buffer instead of the IgG, the bulk of the radioactivity was recovered in the form of intact peptide and only 13.9% in the peak with RT of 10 min. In order to purify the fragments of VIP, unlabelled VIP (50 μg) was treated with 525 μg immune IgG or nonimmune IgG as before, except that bovine serum albumin was omitted from the reaction mixture. The reaction mixtures were extracted on Extract Clean C18 cartridges (Alltech) , and then subjected to reverse phase HPLC on a Novapak-C18 column (Waterε) , eluting with a gradient of acetonitrile in trifluoroacetic acid. The abεorbance of the eluate was monitored at 214 nM. Two A 2 nm absorbing peakε (labeled 1 and 2 in Fig. 6) , noted after treatment of the VIP with immune IgG, were absent in peptide preparations treated with nonimmune IgG or assay buffer. These peaks were purified by a second round of reverse phase HPLC using shallower gradients for elution (Fig. 7 and 8) . The peptide fractionε purified by reverse phase HPLC were dried, and sequenced uεing an Applied Biosyεtems pulsed liquid phase sequenator (model 477A) with on-line phenylthiohydantoin-amino acid detection. Thiε procedure demonstrated unequivocally that the major A^ absorbing peaks identified as 1 and 2 in Fig. 7 and 8, reεpectively, were VIP[1-16] and VIP[17-28]. Faεt atom bombardment (f.a.b.)-mass βpectrometry of peptide 2 in Fig. 8 and intact VIP[1-28] waε performed in the poεitive ion mode on a VG Analytical ZAB-2SE spectrometer (acceleration potential:8kV) (M-Scan) using peptideε dissolved in 5% acetic acid and thioglycerol/glycerol or m-nitrobenzyl alcohol matrices. Mass calibration was performed with cesium iodide or cesium iodide/glycerol. The F.a.b.- asε spectrometric analysiε (Fig. 9) suggested that the molecular mass of peptide 2 was 1393 daltonε corresponding to the molecular ion of VIP[17-28]. It is believed that the additional peak observed with masε of 1415 daltonε probably represented the sodium adduct of VTP[17-28]. Analysis of VIP[1-28] resulted in a signal at 3325 daltons that corresponded well to the molecular ion of the peptide. Amino acid sequencing of the purified fragments produced by hydrolysis of VIP by the autoantibody showed that the scissile bond is Gin 16 - Met 17 (6). Example 5 Induction Of Catalytic Activity In Anti-VIP-Autoantibodv By Removal of Inhibitors A. Ultrafiltration IgG was prepared by chromatography on (i) protein G conjugated to Sepharoεe or (ii) DEAE-celluloεe. The IgG (4 mg/ml) waε ultrafiltered on a YM-10 membrane having an average cut off molecular weight of 10,000 Daltonε uεing an Amicon Model 8 MC apparatuε to 27 mg/ml, diluted back to 0.8 mg/ml and then subjected to a second cycle of ultrafiltration. The final concentration of IgG prepared in this manner was 20 mg/ml. IgG purified as above but without ultrafiltration and IgG purified and with ultrafiltration as above were each incubated with mono( 125 I-Tyr 10 )-VIP in radioimmunoaεsay buffer at 4 β C for two hours in the presence of increasing unlabeled VIP concentrations and the TCA soluble radioactivity waε determined aε described in Example 4. Fig. 10 indicateε that treatment of mono( 125 I, Tyr 10 )-VIP with IgG that had not been εubjected to ultrafiltration reεulted in a doεe-dependent, but low- level degradation of the peptide, judged by the increase in TCA-soluble radioactivity over the value obtained with assay buffer. IgG subjected to ultrafiltration degraded VIP better than IgG which had not been ultrafiltered. B. Dialysis IgG (2mg/ml) , prepared by chromatography as described in A above, was dialyzed using a dialysiε membrane with a cut-off of 12,000-15,000 Daltonε for four dayε againεt 1000 volumeε of buffer (50 mM Tris-HCl, 100 mM glycine, pH 8.0, containing 0.025% Tween-20) , with daily buffer changes (a total of three changes) . Aε with ultrafiltration, IgG εubjected to dialyεiε degraded VIP better than IgG which had not been εubjected to dialyεiε. C. Washing After Immobilization On Protein-G IgG (1 mg in 0.5 ml of buffer (50 mM Tris-HCl, 100 mM glycine, pH 8.0, containing 0.025% Tween-20)) , prepared by chromatography as described in A above, waε applied to a Protein G-Sepharoεe column (settled volume, 3.3 ml) in order to immobilize the IgG on the Protein G. The immobilized IgG was then washed with 135 ml of neutral pH buffer (50 mM Tris-HCl, pH 7.3) followed by elution with a low pH buffer (100 mM glycine-HCl, pH 2.7). The acidic eluent was then neutralized immediately and the IgG isolated. As with ultrafiltration, IgG subjected to neutral buffer washes degraded VIP better than IgG which had not been subjected to such treatment. D. Affinity Chromatography On VIP-Sepharose IgG fractions containing VIP hydrolytic autoantibodies exhibit relatively tight binding of VIP. This property was used to purify specific catalytic VIP hydrolytic autoantibodies on a VIP-Sepharose column. IgG waε purified from the plasma of a human subject by ammonium sulfate precipitation and DEAE-cellulose chromatography (9) . The IgG was free of detectable non- immunoglobulin materials (6) . To prepare the affinity chromatography matrix, synthetic VIP (1-28) (10 mg) mixed with about 20 pg (Tyr 0 - 125 l)-VIP waε covalently coupled to 5g CNBr-Sepharose (5g; Pharmacia) in 0.1M NaHC0 3 , pH7, in 0.5M NaCl for two hours at 4°C, and unreacted groups on the gel were quenched with 0.2M glycine in coupling buffer C 8) . The coupling efficiency was greater than 90%, baεed on incorporation of (Tyr 10 - 125 I)-VIP. About 90 mg IgG waε shaken with 4.5 ml of VIP-Sepharose gel at 4°C and 0.5M Tris-HCL, pH 8.0 for 2 h. The mixture was poured into a column, the gel washed with buffer until the effluent A^ (senεitivity 0.05 AUFS) returned to baseline, and bound IgG was eluted with 0.1 M glycine- HC1, pH 2.7 and neutralized immediately with 1 M Triε- HCl, pH 9.0. Antibody concentrations were estimated by scans (A ) of silver-stained, non-reducing SDS-gels, using authentic IgG as standard (Gilford Response II spectrophotometer) . Increasing authentic IgG concentrations (2-20 ng per lane) showed a linear increase in A^ values. As with ultrafiltration, IgG subjected to affinity chromatography degraded VIP better than IgG which had not been subjected to affinity chromatography. EX*wιp1__ & Preparation Of VIP Homologs Synthetic peptide homologs of VIP were prepared for screening for inhibitory activity. Ten synthetic peptides (Fig. 11) , corresponding to 7-mer, 16- mer and 14-mer linear subsequenceε of VIP, were prepared by solid phase synthesis using methods known in the art (29) at the University of Florida Protein Structure Care Facility, Gainεville, and their identity waε confirmed by amino acid compoεition analyεis. Reverse phase HPLC on a C-18 column revealed a εingle A 214 abεorbing peptide in each of the preparationε. Peptide content of each of theεe preparationε waε >80%. Full length VTP[l-28] waε from Bachem. gxagφl-e 7 Screening Of VIP Homologs For Inhibition Of VIP-Catalytic Autoantibody A. Screening For Binding Activity The ter synthetic peptides were screened for the ability to bind (Tyr 10 - 125 I)-VIP. The peptides were incubated with the autoantibody IgG fraction and (Tyr 10 - 125 I)-VIP in a buffer which was non-permisεive for VIP hydrolysis, i.e., in 7.5 mM sodium phosphate, pH 7.4, 0.64% sodium chloride, 0.5% bovine serum albumin, 25 mM EDTA, 0.005% bacitracin, 0.005% protamine sulfate, 0.073% sodium azide and 0.025% Tween-20. IgG purified from the plasma of a human subject was the source of the autoantibody. Plasma, prepared by centrifugation of blood, was precipitated with 50% saturated ammonium sulfate, the precipitate reconstituted in 50 mM Tris-HCl, pH 8.0, dialyzed against this buffer and IgG purified by chromatography on DEAE- cellulose (9). The IgG showed a εingle silver-stained protein band on SDS-polyacrylamide gels with molecular mass 150 kD, that reacted with peroxidaεe conjugated anti-human IgG in immunoblotε (6) . Scatchard analyεis of IgG-VIP binding suggested that the IgG contained a single type of VIP binding antibody (6) . This conclusion was supported by the observation that a VIP εpecific antibody purified from this IgG preparation was capable of mono-(Tyr 10 - 125 I)-VIP hydrolysis. Affinity purification of the catalytic antibody was by chromatography on VIP coupled covalently to CNBr-Sepharose as described in Example 5. The bound antibodies were eluted with acid (pH 2.7) and brought to neutral pH. Reducing SDS-polyacrylamide gel electrophoresis of this material revealed two silver stained protein bands with maεs 58 kD and 25 kD, εtainable with anti-human H-chain (IgG) and anti-human L- chain antibodies, respectively, in immunoblots. Analytical isoelectric focusing and silver staining on Phastgels (pH gradient 3 to 10; Pharmacia) revealed a series of closely spaced bands with pi 6.8-8.4, indicating a restricted antibody population. The affinity fractionated autoantibodies hydrolyzed (Tyr 10" 125 I)VIP (K„.:0.12 μM) at the same peptide bond (Gin 16 - Met 17 ) as the starting IgG (1) , judged by coelution of the reaction product, (Tyr 10*125 I)VIP(1-16) , with authentic (Tyr 10"125 I)VIP(l-l6) in reverse phase HPLC analyses. Binding assayε were conducted at 4°C for 20 h (6). The amount of (Tyr 10 - 1 5 I)-VIP precipitated by 10% trichloroacetic acid after incubation in buffer and immune IgG was similar (85.6 % and 82.6 % of the total amount of radioactivity available, respectively) , indicating that (Tyr 10 - 125 I)-VIP was not cleaved by the IgG under these conditions. The N-terminal fragment VIP[1-16] at a concentration > 10 -fold larger than (Tyr 10 - 125 I)-VIP failed to displace binding of the radioactive ligand by the autoantibody. In contrast, the c-terminal fragment VIP[15-28] inhibited the binding with potency (K r 1.25 nM) close to that of the full length peptide, VIP[1-28] K g 0.3 nM) (Fig. 12; data, means of duplicates corrected for nonspecific binding observed in the presence of 1 μM VIP, were compiled from these experiments). Saturable binding observed without competitor peptides ranged from 4053 to 6012 CPM, and nonspecific binding waε approximately 600 CPM. The apparent K D or K x for VIP, VIP[15-28] and VIP[22-28] were obtained using the EBDA and LIGAND programs (Elsevier) . It waε assumed that (i) the binding reaction had reached equilibrium, and (ii) K D for (Tyr 10 - 125 I)-VIP and unlabeled VIP was the same. Free energy of binding, ΔF, was computed as: F « - RTInK A , where R is the gas constant at normal temperature and pressure, T is the reaction temperature (277°K) and K A iε the apparent association constant (1/K D or 1/K j ) . K, was computed from the equation Xj** « K„.(1+[I]/K,) , where [I] is the inhibitor concentration. Of the remaining seven shorter peptides tested initially at concentrations of 500 μM each, only VIP[22- 28] and VIP[18-24] inhibited the autoantibody from binding (Tyr 10 - 125 I)-VIP. The K, for VIP[22-28] was 242.1 μM. VIP[22-28] showed approximately 8-fold greater binding potency than VIP[18-24], suggesting that the reactivity of the latter peptide may be due to the shared sequence, VIP[22-24]. Approximate binding energy values for theεe peptideε were, in kcal/mole, VIP[l-28], 12.1; VIP[15-28], 11.3; and, VIP[22-28], 4.6. The binding energy of reεidueε 22-28 was substantial, although only 38% of that for the full length peptide. B. Screening For Inhibition Of Anti-VIP Catalytic Activity By VIPr22-281 Because VIP[22-28] exhibited significant binding to the autoantibody, its ability to inhibit the catalytic activity of the autoantibody waε determined. The hydrolyses of increasing concentrations of VIP in the absence and presence of VIP[22-28] were compared. (Tyr 10 - 125 I)-VIP, 32 pM, was mixed with increasing VIP concentrations and waε treated with the autoantibody, 50 μg IgG, in the absence and presence of VIP[22-28] (100 μM) for three hours at 38 β C. The plot of the reciprocal rate of VIP hydrolysiε verεuε the reciprocal concentration of VIP waε linear, indicating conformity with Michaelis-Menten kinetics (Fig. 13; values were means of duplicates, fitted to the Michaelis-Menten equation by means of the ENZFITTER (Elsevier) program) . The K^ and k cat values for the VIP cleavage in the absence of VIP[22-28] were 115 ± 14 nM and 6.5 ± 0.3 min" 1 , respectively. In the presence of 100 μM VIP[22-28], the apparent , was increased (158.6 ± 4.4 nM) and k cat was unchanged (6.9 ± 0.2 min" 1 ), suggesting competitive inhibition of VIP hydrolysis. K x for VIP[22-28], computed from the equation XJ** > « K,.(1+[I]/K,) , where [I] iε the inhibitor concentration, was 260 μM. Inhibition waε obεerved in the presence of an excess (>300-fold, by weight) of bovine serum albumin. In addition, 400 μM VIP[1-7], a non-binding fragment, did not inhibit VIP hydrolysiε. 6μg VIP[22-28] waε treated with assay diluent or IgG using incubation conditions identical to those employed to hydrolyze VIP[l-28], and the reaction mixture was extracted on a C-18 Seppak cartridge and analyzed by reverse phase HPLC (6) , using a gradient of acetonitrile (8-64% in 45 min) in 0.1 % trifluoroacetic acid. The amountε of VIP[22-28] (retention time « 39.1 min) recovered after incubation in diluent and IgG were not significantly different, judged by the areas of the A 2U absorbing peptide peakε, indicating that VIP[22-28] did not undergo cleavage. VIP[22-28] does not contain the scisεile peptide bond (Gln 16 -Met 17 ) but, as shown by the data above, it bound the autoantibody and inhibited autoantibody catalyzed VIP hydrolysiε. Example 8 Purification And Identification Of Naturally Occurring Inhibitor ts) Of Catalytic Antibodies Directed Against VIP The result of Example 5 prompted the conclusion that each of the four induction methods, i.e., ultrafiltration, dialysis, washing after immobilization on Protein-G and affinity chromatography on VIP- Sepharose, removed a tightly bound inhibitor, thereby imparting VIP hydrolytic activity to the autoantibody. In order to isolate, purify and identify the inhibitor, the ultrafiltrate, dialysate, neutral buffer waεhingε from the Protein-G column or buffer waεhingε from 'che affinity chromatography containing the inhibitor iε concentrated to 3 ml and extracted on a Seppak C-18 Cartridge. Retained material iε eluted with acetonitrile in 0.1% trifluoroacetic acid, dried in vacuo and subjected to reverse phase HPLC on a C-8 or C-18 column. Aliquots of column fractionε are screened for binding activity as deεcribed in Example 7A and for inhibitory activity aε deεcribed in Example 7B by mixing with (Tyr 10 - 125 I)-VlP and catalytic IgG, incubation for 3 h at 38 C and precipitation with 10% trichloroacetic acid. In control tubeε, hydrolysis of the VIP iε meaεured in assay diluent instead of the column fractions. Fractions showing inhibitory activity are pooled and subjected to further Reparation procedures in order to yield the pure inhibitor. These separation procedures include ion exchange chromatography and chromatofocusing (30) . The pure inhibitor iε subjected to amino acid analysis and peptide sequencing on an Applied Biosyεtemε sequenator. Once the identity of the inhibitor is known, it is synthesized in large quantity uεing standard solid phase peptide syntheεis methods (29) . The synthetic inhibitor is then used to specifically inhibit the catalytic autoantibody, resulting in the alleviation of pathogenesis of the autoimmune diεorder (asthma) caused by the catalytic autoantibody (anti-VIP-autoantibody) . Example 9 Characteriiation and Catalytic Activity of IσG Purified By Af inity Chromatography (Fractionation) on V P- A. yip gy yolygjp (Tyr 10 - 125 I)-VIP (about 30 pM) mixed with increasing VIP concentrations waε treated with the IgG or antibodies purified by affinity chromatography on VIP- Sepharose aε in Example 5D for 3 h at 38°C in 200 μl 0.05 M T-is-HCl, 0.1 M glycine, pH 8, containing 0.025% Tween- 20 and 0.1% BSA. The IgG and antibodies tested hydrolysis assays were previously dialyzed against 500 volumes of buffer for 4 days, with daily buffer changeε. Hydrolysis of VIP was computed by measuring the radioactivity rendered soluble in TCA, corrected for the radioactivity observed after incubation in assay diluent (6) . Catalysis by the antibody was determined in the absence and preεence of VIP[22-28]. Data were fitted to the Michaelis-Menten equation by means of the ENZFITTER program (Elsevier) . Reverse phase HPLC of antibody treated reaction mixtures was on a C18 column (6) . B. (τvr 10 - ,25 l) VIP Binding IgG prepared by DEAE-cellulose chromatography was assayed for saturable (Tyr 10 - 125 l)-VIP binding (9), in the absence and presence of increasing concentrations of unlabeled VIP. Apparent K p for VIP was determined using EBDA and LIGAND programs (Elsevier) assuming (i) the binding had reached equilibrium, and (ii) the K g of (Tyr 10 - 125 l)-V P and unlabeled VIP were identical. C. Sodium Dodecylβulfate - Polyacrylamide βel Electrophoreβiβ (SDS-PAGE) and Isoelectric Focusing (IEF) Electrophoresis of antibody preparationε treated with 20 mM M 2-mercaptoethanol and 2.5% SDS (100°C, 5 min) waε on Phaεt SDS-gradient gelε (8-25%) (Pharmacia) . The gel waε stained with silver (31) . For immunostaining, proteins were transferred to nitrocelluloεe (BA85, Schleicher and Schuell) by diffusion blotting (30 min) , the membrane was treated with blocking buffer (0.02 M Tris-HCl, pH 7.4, 0.5 M NaCl, 3% BSA, 0.05% Tween-20) , then with rabbit anti- human H-chain (IgG) (1:1000) or anti-human L-chain (1:2,500) (Accurate) for 60 min, washed with buffer, treated with peroxidase conjugated goat anti-rabbit IgG (1:1000; Accurate), washed again and finally incubated with 0.5 mg iaminobenzidine/ml (Sigma) and 0.03% hydrogen peroxide for 10-30 min. IEF was on Phast IEF gelε using a pH gradient of 3-10 constructed with Pharmalytes. D. Characterisation of Anti-VIP Catalytic Autoantibody (Tyr 10 - 125 I)-VIP to VIP binding waε meaεured using IgG that did not exhibit measurable VIP hydrolytic activity (i.e., IgG which had not been subjected to ultrafiltration, dialysiε, Protein-G chromatography or affinity chromatography on VIP-Sepharoεe) judged by the amount of radioactivity precipitated in 10% TCA after incubation in assay diluent or immune IgG (87.9% and 91.0%). A Scatchard plot of VIP binding by the IgG revealed a single binding component (r«0.99) with K d 0.3 nM and VIP antibody concentration 184 fmol/mg IgG (Fig. 14; values shown in Fig. 14 are means of three replicateε each) . Progressively increasing (Tyr 10 - 12S I)VIP hydrolyεiε by increaεing concentrationε of the affinity-purified antibodieε waε observed, judged by the amount of radioactivity rendered soluble in TCA (Fig. 15) . SDS- PAGE under reducing conditions indicated that the affinity-fractionated material waε composed of 61 kD H- chains and 26 kD L-chains, judged by silver staining and reactivity with anti-H and anti-L chain antibodies in immunoblotε (Fig. 16) . The IEF profile of the affinity- fractionated preparation (pH range 3 * 0-10.5) revealed a restricted range of antibody species (approximately 12 closely spaced bands focused at pH 6.9-8.4), compared to unfractionated IgG (innumerable bands focused mainly at pH 7.1-9.5). E. Hydrolytic Specificity And Catalysis By VIP Antibodies The IgG preparation used here hydrolyzed the Gln 16 -Met 17 bond in VIP (32). Thus, when (Tyr 10 - 125 I)VIP is used as substrate, one radioactive fragment, (Tyr 0 - 1≥5 I)VIP(1-16) , is gen^v.ated. To compare their hydrolytic specificities, lOOμg of unfractionated IgG and 0.3 μg of affinity-purified antibody were incubated with 210 pg (Tyr 10 - 12s I)VlP, and the reaction product characterized by reverse phase HPLC (Fig. 17) . Treatment with both types of antibody preparations generated a single radioactive peptide with retention time identical to that of synthetic 125 I-VIP[1-16] (8.2 min). This radioactive peptide was well reεolved from unhydrolyzed (Tyr 10 - 12δ I)VIP (retention time 21.5 min). Theεe data suggested the peptide generated by the affinity-fractionated antibody and IgG is (Tyr 10 - 125 I)VIP[1-16] and therefore it was concluded that the affinity-purified antibody, like the unfractionated IgG, cleaved the Gln 16 -Met 17 bond. Direct evidence' that the antibody iε a catalyεt waε obtained from the saturation kinetics of VIP hydrolysis. The affinity-fractionated antibody preparation was incubated with increasing VIP concentrations and a fixed (Tyr 10 - 125 I)VIP concentration (30 pM) , and the radioactivity rendered soluble in TCA was measured. Plots of the reciprocal velocity versus reciprocal VIP concentration for affinity fractionated antibodies (66 ng) and for unfractionated IgG (300 μg) were essentially linear, suggesting conformity with Michaeliε-Menton kinetics (Fig. 18) . The K,„ value for the affinity-fractionated antibody waε 110 ± 3 nM, compared to 112 ± 6 nM for unfractionated IgG. The turnover number of the antibody (k Mt ) , computed on the baεiε of the amount of total protein in the assay, was 0.11 ± 0.01 min' 1 . Comparison of the specific activities (V aιaχ /ng total protein) of the affinity-fractionated antibody preparation and unfractionated IgG indicated a 2076-fold purification factor. F. Kinetic study Study of the saturation kinetics displayed by the affinity-purified preparation provided direct evid. *ce tnat the VIP-antibody :Ls a catalyεt. The antibody appeared to bind VIP relatively tightly (K, 110 nM) , compared to conventional peptidases (33) and anti- hapten catalytic antibodies which exhibit , values usually in the micromolar to millimolar range (34). The apparent high affinity εubεtrate binding property of the VIP antibody iε a desirable feature, since it is likely to confer stringent subεtrate εpecificity. Given that peptide bond hydrolyεiε iε an energetically demanding chemical reaction, the calculated valueε of VIP antibody turnover number (k eat 0.11 min *1 ) and kinetic efficiency (k^/K j , 1.1 x 10 6 M "1 min "1 ) are impreεεive. Although the IEF profile of the affinity-fractionated VIP antibodieε revealed a restricted range of antibodies, it remains poεsible that the preparation may not be a homogeneous one. Thuε, the k Mt meaεured for the affinity- fractionated antibody preparation (0.11 min" 1 ) iε a minimal value. The theoretical k Mt value of the VIP antibody present in unfractionated IgG (V iβχ /amount of antibody, estimated from aε the x-intercept of the Scatchard plot) waε 6.5 min' 1 . In comparison, the k Mt and -fc cat /K* values reported for an amidase antibody raised against a presumed transition state analog are 0.08 min *1 and 1.4 x 10 2 M" 1 min * \ respectively (35). An antibody capable of Gly-Phe bond cleavage with metal co-factor asεiεtanσe iε purported to be a true catalyst with k eat 0.04 min' 1 , but its saturation kinetics are not described (36). Other embodiments of the invention will be apparent to those skilled in the art from a consideration of this specification or practice of the invention disclosed herein. REFERENCES 1. Pauling, L. Nature 161:707, 1948. " \ . Kohen, F. , Kim., J.B., Lindner, H.R., Eshhar, Z. , Green, B. Antibody enhanced hydrolyεiε of steroid esters FEBS Lett. 111:427 (1980). 3---Pollack, S.J^ Jacobs, J.W., Schultz, P.G. Science 234, 1570 (1986); A. Tramontano, A.A. Amman, R.A. Lerner, J. Am. Chem Soc. 110, 2282 (1988); K.D. Janda, D. Schloeder, S.J. Benkovic, R.A. Lerner, Science 241: 1188 (1988); C.N. Durfor, R.J. Bolin, R.J. Sugasawara, R.J. Maεsey, J.W. Jacobs, P.G. Schultz, J. Am. Chem. Soc. 110: 8713 (1988). 4. Jackεon, * ^.Y., Jacobs, J.W. , Sugasawara, R. Reich, S.H., Bartlett, P.A. , Schultz, P.G., J. Am. Chem. Soc. 110: 4841 (1988); D. Hilvert, S.H. Carpenter, K.D. Nared, N.T. Auditor, Proc. Natl. Acad. Sci. USA 85: 4953 (1988). 5. Shokat, K, Leumann, C.H., Sugasawara, R. , Schultz, P.G., Anoew. Chem. Int. Ed. Enol. 27: 1172 (1988). 6. Paul, S. et al.. Catalytic hydrolyεiε of vaεoactive inteεtinal peptide by human autoantibody. Science 244:1158-1161 (1989). 7. Paul, S., H. Erian, P., Said, S.I. Autoantibody to vaεoactive intestinal peptide in human circulation. Biochem. Biophys. Reε. Commun. 130:479-485 (1985). 8. Paul, S., Said, S.I. Human autoantibody to vaεoactive inteεtinal peptide: Increased incidence in muscular exercise. Life Sciences 43:1079-1084 (1988). 9. Paul, S., Said, S.I., Thompson, A., Voile, D.J., Agrawal, D.K. , Foda, H. , De la Rocha, S.: Characterization of autoantibodieε to VIP in aεthma. J. Neuroimmunol. 23:133-142 (1989). 10. Itoh, N., Obata, K.-I., Yanaihara N. , Okamoto, H. Human preprovaεoactive inteεtinal polypeptide containε a novel PHI-27-like peptide, PHM-27, Nature 304:547-549 (1983). 11. Bloom, S.R. , Barnes, A.J., Adrian, T.E., Polak, J.M. Autoimmunity in diabeticε induced by hormonal contaminantε of inεulin. Lancet 1:14-17 (1979). 12. Ruff, M.R., Martin, B.M. , Ginns, E.I., Farrar, W.L. , Pert, C.B. CD4 receptor binding peptides that block HIV infectivity cause human monocyte chemotaxis. FEBS Lett. 211:17-22 (1987). 13. Nilsson, A. Structure of the vasoactive inteεtinal peptide from chicken intestine. The amino acid sequence. FEBS Lett. 60:322-326 (1975). 14. Dimaline, R. , Thorndyke, M.C. Purification and characterization of VIP from two species of dogfish. Peptides 7(Suppl.l) :21-26 (1986). 15. Paul, S. , Chou, J. , Beckham, S., Liu, L.- W, Kubota, E., Dominguez, N. , Said, S.I Elevated levels of atrial natriuretic peptide and vaεoactive intestinal peptide in exercising man. Clip. Res, (abεtr.) 35:112A (1987). 16. Woie, L., Kaada, B., Opεtaad, P.K. Increase in plasma VIP in muscular exercise. Gen. Pharmacol. 17:321-326 (1987). 17. Rosεelin, G. The receptorε for the VIP family peptideε (VIP, secretin, GRF, PHI, PHM, GIP, glucagon and oxyntomodulin) . Specificites and identity. Peptideε 7fSupol. 1):89-100 (1986). 18. Paul, S., Said, S.I. Characterization of receptorε for vaεoactive inteεtinal peptide from the lung. J. Biol. Chem. 262:158-162 (1987). 19. Barret, A.J. and Salveεen, A., edε., Proteinaεe Inhibitors. Elsevier, London (1986) ; Meek, L.D. et al., "Inhibition of HIV-l Protease In Infected T- Lymphocytes By Synthetic Analogueε", Nature 343: 390-392 (1990). 20. Amit, A.G., Mariuzza, R.A. , Philipε, S.E.V. , Poljak, R.J., Science 233: 747 (1986); S. Sheriff, et al., Proc. Natl. Acad. Sci. fUSA^ 84: 8075 (1987). 21. van Regenmortel, R.H.V. , Synthetic Peptideε aε Antigens. Laboratory Techniques in Biochemistry and Molecular Biology Series, (Eds: R.H. Burdon and P.H. van Knippenberg, 19: 1-39 (1988). 22. Benjamini, E. , Shimizu, M. , Young, J.D., Leung, C.Y., Biochemistry. 7: 1261 (1968); E. Benjamini, M. Shimizu, J.D. Young, C.Y. Leung, ibid. 7: 1253 (1968). 23. Barrett, A.J., Proteinase Inhibitors. (Edε. A.J. Barrett and G. Salvesen, Elsevier, 3-22 (1986) . 24. Rich, D.H., Proteinase Inhibitorε. (Eds. A.J. Barrett and G. Salvesen, Elsevier, 179-217 (1986) . 23: 133 26. Paul, S., Wood, K. , Said, S.I. Purification of [ 125 I]-Vasoactive inteεtinal peptide by reverse-phase HPLC. Peptides 5:1085-1087 (1984). 27. Turner, J.T., Bylund, D.B. Characterization of the VIP receptor in rat submandibular gland: Radioligand binding asεay in membrane preparations J. Pharmacol Exp. Therap. 242:873-881 (A..87). 28. Affinity Chromatography. Principles and Methods. Pharmacia, Uppsala, Sweden, 12-18 (1986) . 29. (Stewart, J.M. and Young, J.D., Solid Phaεe Peptide Syntheεiε. 'Pierce Chemical Co., Rockford, Illinoiε (1984). 30. FPLC™ Ion Exchange and Chromatofocusing, Pharmacia, Uppsala, Sweden, 1-171 (1985) . 31. PhastGel Silver Kit Instruction Manual. Pharmacia (Uppsala, Sweden 1987) . 32. Baldwin, E. and Schultz, P.G., Generation of a catalytic antibody by εite-directed mutageneεiε. Science. 244:1152 (1989). 33. Dixon, M. , Webb, E.C. et al., Enzymeε. 3d Ed. Longman, (London 1979) ; Fiεher, G. Acyl group tranεfer-Aεpartic proteinaεeε. Enzv e Mechaniεmε. M.I. Page and A. Williams, edε.. Royal Society of Chemistry, 230 (London 1987) . 34. Janda, K.D. et al., pupra ref. 3; Schultz, P.G. Catalytic antibodies. Ace. Chem. Res. 22:287 (1989); Blockburn, G.M. , Kang, A.S. et al. Catalytic antibodies. Biochem. J. 262:381 (1989). 35. Janda, K.D. et al., supra ref. 3. 36. Iversen, B.L. and Lerner, R.A., Science 243:1184 (1989).

Claims: We claim: 1. An inhibitor which inhibits an antibody from catalyzing a chemical reaction of a substrate, said inhibitor comprising (a) a fragment of the substrate, (b) an analog of a fragment of the substrate or (c) an analog of the substrate, provided that said inhibitor was not used to elicit said catalytic antibody. 2. An inhibitor which inhibits an autoantibody from catalyzing a chemical reaction of a substrate. 3. An inhibitor which inhibitε a firεt antibody from catalyzing a chemical reaction of a substrate, said inhibitor comprising a second antibody which is antiidiotypic to said firεt antibody. 4. An inhibitor as recited in claim 1, wherein said chemical reaction is the cleavage or formation of a bond in said subεtrate. 5. An inhibitor aε recited in claim 4, wherein said bond iε a peptide bond. 6. An inhibitor as recited in claim 1, wherein said substrate is selected from the group consisting of a peptide, a protein, a hormone, a neurotransmitter and a neurohumoral factor. 7. An inhibitor as recited in claim 2, wherein said substrate iε a self-antigen of an animal having said autoantibody. 8. An inhibitor as recited in claim 2, wherein said substrate is selected from the group consisting of a peptide, a protein, a hormone, a neurotransmitter and a neurohumoral factor. 9. An inhibitor as recited in claim 8, wherein said substrate is a peptide. 10. An inhibitor as recited in claim 9, wherein said substrate is VIP. 11. An inhibitor aε recited in claim 9 wherein said fragment of said substrate is a homologous peptide. 12. An inhibitor capable of inhibiting anti- VIP catalytic auto-antibody from catalyzing a cleavage of the Gln 16 -Met 17 peptide bond in VIP, said inhibitor comprising VIP[22-28] . 13. An inhibitor which inhibits anti-VIP catalytic autoantibody from catalyzing a cleavage of the Gin 16 - Met 17 peptide bond in VIP, said inhibitor having been prepared by a procesε comprising the steps of: (a) collecting serum from an animal having said autoantibody; (b) separating the gamma globulin fraction from said serum; (c) separating from said gamma globulin fraction molecules which bind to said gamma globulin; and (d) screening said molecules to identify a molecule(s) which is capable of binding to and thereby inhibiting said autoantibody from catalyzing said cleavage. 14. An inhibitor as recited in claim 14 wherein said molecules which bind to said gamma globulin are separated from said gamma globulin by ultrafiltration. 15. An inhibitor as recited in claim 14 wherein said molecules which bind to said gamma globulin are separated from said gamma globulin by dialysis. 16. An inhibitor as recited in claim 14 wherein said molecules which bind to said gamma globulin are separated from said gamma globulin by chromatography on Protein G-Sepharose. 17. An inhibitor aε recited in claim 14 wherein said molecules which bind to said gamma globulin are separated from said gamma globulin by affinity chromatography on VIP-Sepharose. 18. A method for preparing an inhibitor which inhibits an antibody from catalyzing a chemical reaction of a substrate but which was not itself used to elicit said antibody, said method comprising the steps of: (a) synthesizing one or more fragments of the substrate; or (b) synthesizing one or more analogs of one or more fragments of the substrate; or (c) synthesizing one or more analogs of said substrate; and (d) screening said fragment(β) or analog(ε) synthesized in steps (a)-(c) to identify a fragment(s) or analog(s) which inhibits said antibody. 19. A method for preparing an inhibitor which inhibits an autoantibody from catalyzing a chemical reaction of a substrate comprising the steps of: (a) collecting serum from an animal having said autoantibody; (b) separating the gamma globulin fraction from said serum; (c) separating from said gamma globulin fraction molecules which bind to said gamma globulin; and (d) screening said molecules to identify a molecule(ε) which iε capable of inhibiting said autoantibody. 20. A method aε recited in claim 19, wherein said molecule is a lower molecular weight molecule which is separated from said gamma globulin fraction by ultrafiltration or by dialysiε. 21. A method as recited in claim 19, wherein said molecule(s) is separated from said gamma globulin fraction by chromatography or a non-specific protein support or by affinity chromatography on a protein support specific for said autoantibody. 22. A method for preparing an inhibitor which inhibits an autoantibody from enhancing the rate of cleavage or formation of a bond contained in a substrate comprising the steps of: (a) synthesizing one or more analogs or one or more fragments of said substrate; and (b) screening said analog(s) or said fragment(ε) to identify an analog(s) or fragment(ε) which inhibitε said autoantibody. 23. A method for preparing an inhibitor which inhibits a first antibody from catalyzing a chemical reaction of a substrate comprising the steps of: (a) generating a plurality of antibodies to said first antibody; and (b) screening said plurality to identify a second antibody which is capable of binding to and thereby inhibiting said first antibody, said second antibody being antiidiotypic to said first antibody. 24. A method as recited in claim 23, wherein said plurality is generated by: (a) immunizing an animal with said first antibody thereby generating antibody-producing lymphocytes in said animal; (b) removing said antibody-producing lymphocytes from said animal; and (c) fusing said antibody-producing lymphocytes with myeloma cellε and thereby producing a plurality of hybridoma cellε each producing monoclonal antibodieε. 25. An inhibitor which inhibitε an antibody from catalyzing a chemical reaction of a εubεtrate, εaid inhibitor having been prepared by a process comprising the steps of: (a) synthesizing one or more fragments of the substrate; or (b) synthesizing one or more analogs of one or more fragments of the substrate; or (c) synthesizing one or more analogs of said substrate; and (d) screening said fragment(s) or analog(ε) synthesized in steps (a)-(c) to identify a fragment(ε) or analo (s) which inhibits said antibody, provided that said inhibitor was not used to elicit said catalytic antibody. 26. An inhibitor which inhibits an autoantibody from catalyzing a chemical reaction of a substrate, said inhibitor having been prepared by a process comprising the steps of: (a) collecting serum from an animal having said autoantibody; (b) separating the gamma globulin fraction from said serum; (c) separating from said gamma globulin fraction molecules which bind to said gamma globulin; and (d) screening εaid molecules to identify a molecule(s) which is capable of inhibiting said autoantibody. 27. A method as recited in claim 26, wherein said substrate is a peptide and said chemical reaction is the cleavage of a bond in said peptide. 28. A method as recited in claim 27, wherein said autoantibody is anti-VIP catalytic autoantibody, said peptide is VIP and said bond is the Gin 16 - Met 17 bond. 29. An inhibitor which inhibits an autoantibody from catalyzing a chemical reaction of a substrate, said inhibitor having been prepared by a process comprising the steps of: (a) synthesizing one or more analogs or one or more fragments of said substrate; and (b) screening said analog(ε) or fragment(s) to identify an analog(ε) cr a fragment(s) which inhibits said autoantibody. 30. An inhibitor aε recited in claim 29, wherein said substrate is a peptide and said chemical reaction is cleavage of a bond in said peptide. 31. An inhibitor as recited in claim 30, wherein said autoantibody is anti-VIP catalytic autoantibody, said peptide is VIP and said bond is the Gin 16 - Met 17 bond. 32. An inhibitor as recited in claim 31, wherein said fragment which inhibits anti-VIP catalytic autoantibody iε VIP[22-28]. 33. An inhibitor which inhibits a first antibody froon catalyzing a chemical reaction of a substrate, said inhibitor comprising a second antibody which is antiidiotypic to said first antibody, εaid second antibody having been prepared by a procesε comprising the steps of: (a) generating a plurality of antibodies to said first antibody; and (b) screening 'said plurality to identify said second antibody which is capable of binding to and thereby inhibiting said first antibody. 34. An inhibitor as recited in claim 23 wherein said plurality is generated by: (a) immunizing an animal with said firεt antibody thereby generating antibody-producing lymphocyteε in said animal; (b) removing said antibody-producing lymphocytes from said animal; and (c) fusing εaid antibody-producing lymphocyteε with myeloma cellε and thereby producing a plurality of hybridoma cellε each producing monoclonal antibodieε. 35. A method for inhibiting an antibody from catalyzing a chemical reaction of a substrate comprising contacting said antibody with an effective amount of inhibitor under conditions suitable for said inhibition to take place, said inhibitor having been prepared by a process comprising the steps of: (a) synthesizing one or more fragments-of the substrate; or (b) synthesizing one or more analogs of one or more fragments of the substrate; or (c) synthesizing one or more analogs of said substrate; and (d) screening said fragment(s) or analog(s) synthesized in steps (a)-(c) to identify a fragment(s) or analog(s) which inhibits said antibody, provided that said inhibitor was . used to elicit said catalytic antibody. 36. A method for inhibiting an autoantibody from catalyzing a chemical reaction of a substrate comprising contacting said autoantibody with an effective amount of an inhibitor under conditions suitable for said inhibition to take place, said inhibitor having been prepared by a process comprising the steps of: (a) collecting serum from an animal having said autoantibody; (b) separating the gamma globulin fraction from said serum; (c) separating from said gamma globulin fraction molecules which bind to said gamma globulin; and (d) screening said molecules to identify a molecule(s) which is capable of inhibiting said autoantibody. 37. A method for inhibiting an autoantibody from catalyzing a chemical reaction of a substrate comprising contacting said autoantibody with an effective amount of an inhibitor under conditions suitable for said inhibition to take place, said autoantibody having been prepared by a process comprising the steps of: (a) synthesizing one or more analogs or one or more fragments of said substrate; and (b) screening said analog(ε) or fragment(ε) to identify an analog(ε) or a fragment(s) which inhibitε said autoantibody. 38. A method for inhibiting a first antibody from catalyzing a chemical reaction of a substrate comprising contacting said first antibody with an effective amount of a second antibody under conditions suitable for said inhibition to take place, said second antibody being antiidiotypic to said first antibody, said second antibody having been prepared by a procesε comprising the steps of: (a) generating a lura)ity of antibodies to said first antibodies; and (b) screening said plurality to identify said second antibody which is capable of binding to and thereby inhibiting said first antibody. 39. A method for treating autoimmune diseaεe in an animal wherein an autoantibody, which catalyzeε a chemical reaction of a εubεtrate in said animal, contributes to or iε reεponεible for the pathophyεiology of said autoimmune diseaεe aε a reεult of said reaction being catalyzed, said method comprising the step of administering to said animal or to a fluid of said animal an inhibitor which inhibits said autoantibody from catalyzing said chemical reaction. 40. A method for treating autoimmune diseaεe in an animal wherein an autoantibody, which catalyzeε a chemical reaction of a εubεtrate in said animal, contributes to or iε reεponεible for the pathophyεiology of said autoimmune diseaεe aε a reεult of said reaction being catalyzed, said method comprising the steps of: (a) synthesizing one or more fragments of the substrate; or (b) synthesizing one or more analogs of one or more fragments of the εubεtrate; or 61 (c) synthesizing one or more analogs of said substrate; or (d) screening said fragment(s) or analog(ε) synthesized in steps (a)-(c) to identify a fragment(s) or analog(s) which inhibits said autoantibody; and (e) administering said inhibitor to an animal afflicted with said autoimmune disease or to a fluid of said animal. 41. A method for treating autoimmune disease in an animal wherein an autoantibody, which catalyzes a chemical reaction of a substrate in said Animal, contributes . o or iε responsible for the pathophysiology of said autoimmune diseaεe aε a result of said reaction being catalyzed, said method comprising the steps of: (a) collecting serum from an animal having said autoantibody; (b) separating the gamma globulin fraction from said serum; (c) separating from said gamma globulin fraction molecules which bind to said gamma globulin; (d) screening said molecules to identify a molecule(s) which is capable of binding to and thereby inhibiting said autoantibody from catalyzing said chemical reaction of said substrate; and (e) administering a compound(s) identified in step (d) to an animal afflicted with said autoimmune disease or to a fluid of said animal. 42. A method for treating autoimmune disease in an animal wherein an autoantibody, which catalyzes a chemical reaction of a substrate in said animal, contributes to or is responεible for the pathophysiology of said autoimmune diseaεe as a result of said reaction being catalyzed, said method comprising the step of administering to said animal or to a fluid of said animal an inhibitor which inhibits said autoantibody from catalyzing said chemical reaction, said inhibitor having been prepared by a procesε compriεing the steps of: (a) synthesizing one or more fragments of the substrate; or (b) synthesizing one or more analogs of one or more fragmentε of the substrate; or (c) synthesizing one or more analogs of said substrate; and (d) screening said fragment(s) or analog(s) synthesized in steps (a)-(c) to identify a fragment(s) or an analog(ε) which inhibitε said autoantibody. 3 . A method for treating autoimmun e disease in an animal wherein an autoantibody, which catalyzes chemical reaction of a substrate in said animal, contributes to or iε reεponεible for the pathophyεiology of said autoimmune diseaεe as a reεult of said reaction being catalyzed, εaid method compriεing the step of administering to an animal afflicted with said autoimmune disease or to a fluid of said animal an inhibitor which inhibits said autoantibody from catalyzing said chemical reaction, said inhibitor having been prepared by a process comprising the stepε of: (a) collecting εerum from an animal having said autoantibody; (b) separating the gamma globulin fraction from said serum; (c) separating from εaid gamma globulin fraction molecules which bond to εaid gamma globulin; and (d) screening said molecules to identify a molecule(s) which iε capable of binding to and thereby inhibiting said autoantibody from catalyzing said chemical reaction of said substrate. 44. A method as recited in claim 38, wherein said autoimmune disease is selected from the group consisting of asthma, bronchitiε, diabeteε and impotence. 45. A method as recited in claim 38, wherein said substrate is selected from the group consisting of a peptide, a protein, a hormone, a neurotransmitter and a neurohumoral factor. 46. A method as recited in claim 41, wherein said autoimmune disease is asthma, said substrate is VIP and said analog of VIP is a homologous peptide. 47. A pharmaceutical composition for treating autoimmune disease in an animal wherein an autoantibody, which catalyzes a chemical reaction of a substrate in said animal, contributes to or iε responsible for the pathophysiology of said autoimmune disease as a result of said reaction being catalyzed, said composition comprising (a) an inhibitor which inhibits said autoantibody from catalyzing a said chemical reaction, and (b) a pharmaceutically suitable carrier. 48. A pharmaceutical composition for treating asthma which comprises an inhibitor of anti-VIP catalytic autoantibody and a suitable pharmaceutical carrier.

Inventors: MASSEY RICHARD J, PAUL SUDHIR, POWELL MICHAEL J, MASSEY, RICHARD, J., PAUL, SUDHIR, POWELL, MICHAEL, J.
Applicants: IGEN INC, IGEN, INC.
Application year: 1991
Main classification: A61K37
IPC codes: A61K35, A61K38, A61K39, A61P3, A61P11, A61P13, A61P15, A61P37, C07K1, C07K7, C07K14, C07K16, C12N9, C12P21, G01N33