bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monoclonal autoantibodies from insulin-dependent diabetic patients: autoantibodies against β-cell surface or cytoplasmic antigens
Authors: HOUSSAINT E , POGU S , OUARY M , SAI P 
Published: July 2010

SUMMARYTo investigate the target antigen(s) recognized during the autoimmune process in insulin-dependent diabetes mellitus (IDDM), we produced human monoclonal antibodies by Epstein-Barr virus transformation of peripheral blood lymphocytes from a large number (n= 50) of newly diagnosed IDDM patients. Screening by indirect immunofluorescence assay, using the RINm5F rat insulinoma cell line and eight other human or rat tumour cell lines, was performed to identify monoclonal antibodies that reacted with either membrane or cytoplasmic antigens. Eighteen IgM monoclonal antibodies reacting with cytoplasmic antigens of RIN cells were obtained; 14 of them also showed a staining of the cytoplasm of various non-β-cell lines, while four displayed a binding restricted to β-txlls among the panel tested. However, among three monoclonal antibodies reacting with the membrane of RIN cells, one (HMD-1) produced an IgG antibody with a binding restricted to the membrane of β-cells (RIN, HIT, and normal rat islet cells). The membrane antigens of HMD-1 were identified in Western blotting as proteins with molecular weights of 64 and 70 kD. This antibody had no apparent cytotoxic effect on RIN cells. These data suggest that, apart from ‘natural autoantibodies,’ it is feasible to obtain human monoclonal antibodies from IDDM patients that bind specifically to the β-cell cytoplasm or to the β-cell membrane.
Autoantibodies to crude human leucocyte interferon (IFN), native human IFN, recombinant human IFN-alpha 2b and human IFN-gamma in healthy blood donors
Authors: ROSS C , HANSEN M B , SCHYBERG T , BERG K 
Published: July 2010

SUMMARYRecently, naturally occurring antibodies to IFN-α were discovered in a few systemic lupus erythematosus (SLE) and cancer patients; however, in most patients monitored for anti-IFN antibodies before treatment, no antibodies were found. In an attempt to explain the ‘IFN-blocking effect’ that we observed in all serum samples we investigated 200 sera from healthy blood donors. We isolated the globulin fraction, and used rabbit anti-human IgG and IgM columns, protein A columns and T-gel affinity chromatography to isolate human IgG and IgM. All sample fractions were tested in a biological IFN neutralization assay by means of a sensitive MTT-assay. We found that normal human serum contained autoantibodies to crude human leucocyte IFN, native human fibroblast IFN, recombinant human leucocyte IFN-α2b and recombinant human IFN-γ, and that these naturally occurring antibodies were biologically active immunoglobulins of IgG and IgM type. These anti-IFN antibodies were also present in purified human normal immunoglobulin pools. We conclude that all humans have naturally occurring anti-interferon antibodies in their serum, and it is a tempting theory that human cytokines and lymphokines are, at least partly, regulated by immunoglobulins.
Thyroid follicular cell function after non-lethal complement membrane attack
Authors: WEETMAN A P , FREEMAN M , MORGAN B P 
Published: July 2010

SUMMARYTerminal complement complexes have been identified around thyroid follicles in Graves' disease and Hashimoto's thyroiditis. and the concentrations of such complexes are increased in the sera of these patients, suggesting a role for complement activation and membrane attack complexes (MAC) in autoimmune thyroiditis. This has been investigated further using cultured human and rat thyroid cells. Thyrocytes were resistant to lysis by homologous complement, in contrast to the effects of heterologous (rabbit) complement. The formation of non-lethal amounts of MAC, using reactive lysis or classical pathway activation, significantly reduced cAMP production by these cells in response to thyroid-stimulating hormone (TSH) (P&lt;0.01); similar effects were seen with thyroid-stimulating antibodies. Thyroid cells were able to recover rapidly from complement attack after washing and incubation for 30 min. Non-lethal MAC formation also resulted in reactive oxygen metabolite production, detected by luminol-dependent chemiluminescence in three out of five thyroid cell preparations tested, Ionomycin, but not TSH. also stimulated reactive oxygen metabolite production. These results suggest that repeated or continuous sub-lethal complement attack on thyroid cells may exacerbate hypothyroidism in Hashimoto's thyroidilis, or partially counter the effects of thyroid-stimulating antibodies in Graves' disease. Furthermore, the production of reactive oxygen metabolites in these circumstances could increase the intra-thyroidal inflammatory response; oxygen radical scavenging by anti-thyroid drugs (which are concentrated by thyrocytes) may account in part for the amelioration of thyroidilis observed with such treatment.
Degradation of human myelin in vitro by leucocytes from patients with multiple sclerosis
Authors: OWEN S J , WATSON C M , DAVISON A N 
Published: July 2010

SUMMARY
In order to study the possible autoimmune basis of multiple sclerosis (MS) a quantitative method has been used to investigate breakdown of human myelin in vitro. We found that serum from MS patients and controls was generally devoid of any myelin degradative activity. However, isolated peripheral blood mononuclear cells from 43% of MS patients showed significant myelin degradative activity as did those from 61.5% of patients with rheumatoid arthritis (RA). Myelin degradation by cells was found in only 13% of patients with other neurological diseases and in no healthy controls. It is proposed that this non-specific peripheral cellular immune degradative activity originates from cells activated within the central nervous system of MS patients or the joints of individuals with RA. As a result, activity in the blood only indirectly reflects the ongoing inflammatory response at the primary site, accounting for the lack of correlation between changes in the blood and the clinical status of the MS patient. We further propose that the lack of in vitro myelin degradative activity in cells recovered from the cerebrospinal fluid is due to autoaggressive cells being sequestered to the brain.
Isolation and characterization of a high molecular weight lymphocyte Feγ receptor-blocking factor associated with renal allograft survival
Authors: SANDILANDS G P , COCKER J E , McMILLAN M A , OWSIANKA A M , MARSDEN H , JUNOR B J R , BRIGGS J D , MACSWEEN R N M 
Published: July 2010

SUMMARYWe have confirmed our previous observation that improved human renal allograft survival is associated with the presence in pre-transplant serum of a high molecular weight lymphocyte Fey receptor-blocking factor. Serum fractionation studies suggest that this factor is a complex protein consisting of IgG together with an IgG-binding protein which has an apparent molecular weight of approximately 60 kD.
In vivoboosting of lung natural killer and lymphokine-activated killer cell activity by interleukin-2: comparison of systemic, intrapleural and inhalation routes
Authors: FLEXMAN J P , MANNING L S , ROBINSON B W S 
Published: July 2010

SUMMARYNatural killer (NK) cells are thought to play a role in host defence against malignancy and infection, in immunoregulation and as precursor cells in a generation of lymphokine-activated killer (LAK) cells which can lyse NK-resistant tumour cells. As the lung is a major site for malignancy and infection and as there are large numbers of lymphoid cells including NK cells in the interstitial compartment of the lung, we evaluated the capacity of interleukin-2 (1L-2), a lymphokine capable of augmenting NK activity in vitro, to augment lung NK cell activity in vivo, usingdifferent routes ofIL-2 administration. We compared both systemic (i.v. and i.p.) and local (intrapleural and inhalation) routes of IL-2 administration (50000 UJdaily for 5 days) using CBA mice, assessing NK and LAK cell activity in the spleen (systemic) and in the lung. The target cells used for these studies were the YAC-1 (NK-sensitive) and P815, NO36 and HA56 (NK-resistant, LAK-sensitive) cell lines. Splenic NK activity was increased by 1.4-1 1.9-fold for i.v./i.p., respectively, compared with controls with both systemic routes of administration, and lung NK activity was increased 3-2-fold and 3-8-fold (i.v./i.p, respectively, P &lt; 0.05), to levels which were comparable to systemic (splenic) NK activity following the same therapy. Intrapleural IL-2 administration similarly enhanced lung NK activity (3-3-fold) and splenic NK activity (1.3-fold; P&lt;0.05 versus controls for both). Surprisingly, inhaled IL-2 suppressed both splenic and lung NK cell activity (84.8% and 78 ± 10% suppression, respectively, P&lt;0.05). LAK cell activity was also enhanced in the lung by 1.8-8-fold in response to i.v., i.p. and intrapleural IL-2, whereas inhaled IL-2 was ineffective in generating LAK cell activity. These results suggest that the systemic and intrapleural administration of IL-2 effectively boost pulmonary NK and LAK activity whereas inhalation of IL-2 does not. Thus, in clinical situations where boosting of local lung NK or LAK cell activity is desired, these routes of IL-2 administration may be effective.
A novel strategy for targeting CD4+ PPD-reactive T cells against tumour cells using PPD monoclonal antibody heteroconjugates
Authors: MONTGOMERY A M P , WING M G , LACHMANN P J 
Published: July 2010

SUMMARYWe have constructed PPD monoclonal antibody heteroconjugates specific for a tumour-associated antigen of C57BL/6 melanomas or for human complement component C3d fixed de novo to murine fibrosarcoma cells (MC6A). The ability of our heteroconjugates to target CD4+ PPD-reactive T cells against the appropriate tumour targets was then determined in vitro. Heteroconjugate-treated B16-F10 and MC6A tumour targets were both able to present PPD to the specific T cells, resulting in activation and concomitant tymphokine secretion. Secreted lymphokines were then demonstrated to cause significant tumour cytolysis and cytostasis in vitro. Preliminary experiments in vivo suggest that this targeting system may provide the basis for a future immunotherapeutic strategy.
Titration of antibodies against neutrophil cytoplasmic antigens is useful in monitoring disease activity in systemic vasculitides
Authors: EGNER W , CHAPEL H M 
Published: July 2010

SUMMARY
Titration of antibodies against neutrophil cytoplasmic antigens (cANCA), as detected by indirect immunofluorescence. is shown to be clinically useful for monitoring disease activity in Wegener's granulomatosis and microscopic polyarteritis. Ten patients were followed (eight from presentation) prospectively for up to 2 years; during this lime there were six episodes of vasculitic relapse in four patients and five infective episodes and one pulmonary embolus in four patients. Titres of cANCA were markedly raised, both at presentation (1 /32–1/2048) and at vasculitic relapse (1/125–1/1048) but not in infection or embolism (negative. 1/16). Thus the titre of these antibodies can distinguish non-vasculitic illness from vasculitic relapse, in contrast to C-reactive protein levels which were raised in both. Titres of cANCA fell gradually after vasculitic relapse, in keeping with the half-life of IgG (3 weeks). C-reactive protein is a better measure of recovery.
Purification and characterization of IgG immunoconglutinins from patien with systemic lupus erythematosus: implications for a regulatory functiot
Authors: NILSSON B , EKDAHL K NILSSON , SVARVARE M , BJELLE A , NILSSON U R 
Published: July 2010

SUMMARYThe levels of IgG immunoconglutinins in plasma from patients with rheumatoid arthritis, systemic lupus erythematosus and primary biliary cirrhosis were monitored by ELISA. High levels of IgG immunoconglutinins were found mainly in plasma from patients with systemic lupus erythematosus. These immunoconglutinins bound to microtitre plate-fixed C3, C3b and C3c but poorly to C3d. This binding was inhibited by particle-bound C3b and iC3b but not by the corresponding soluble fragments. Furthermore, Western blot analysis revealed no immunoconglutinin-binding to reduced C3 peptides and no binding was shown to soluble C3 α and β chain by ELISA. IgG immunoconglutinins were purified from three plasma specimens by affinity chromatography on activated thiol sepharose ATS/C3 fragments. Two immunoconglutinin preparations that preferentially recognize ATS-C3b, inhibited C5-converlase function by 50–100% while one immunoconglutinin that recognized ATS-C3d,g had no effect. The two former immunoconglutinins also inhibited all three factor I cleavages in C3α chain but the latter inhibited only the third cleavage. None of the immunoconglutinins affected the binding of complement-coated anti-BSA/BSA complexes to CRI (CD 35) on human erythrocytes, but the two immunoconglutinins that inhibited all factor I cleavages also inhibited the factor I-induced release of anti-BSA/BSA complexes from CRI. The results show that immunoconglutinins recognize specific epitopes on bound C3 fragments and that they are able to modulate C3-mcdiated functions.
Anti-heparan sulphate reactivity in sera from patients with systemic lupus erythematosus with renal or non-renal manifestations
Authors: TERMAAT R M , BRINKMAN K , NOSSENT J C , SWAAK A J G , SMEENK R J T , BERDEN J H M 
Published: July 2010

SUMMARYPreviously, we have shown that anti-DNA can bind to heparan sulphate (HS). a constituent of the glomerular basement membrane (GBM). We hypothesized that binding of anti-DNA to HS in the GBM plays a role in the onset of systemic lupus erythematosus (SLE) nephritis. To test this hypothesis we measured the anti-HS reactivity in cross-sectional and longitudinal studies of SLE patients with or without nephritis. In the transverse serum study single serum samples from 26 SLE patients were studied. We found no correlation between anti-HS reactivity and previous development of nephritis (anti-HS positive: seven out of 16 with history of nephritis, two out of 10 without nephritis). However, six of the seven anti-HS positive sera in the nephritis group were obtained within 1 month of the onset of nephritis, suggesting a temporal relationship between anti-HS reactivity and onset of nephritis. In the longitudinal serum study between six and 16 serum samples were studied from each of 10 SLE-patients. In five out of five episodes of nephritis we found anti-HS reactivity before the onset or exacerbation of the nephritis. In four non-renal manifestations anti-HS reactivity was found in only one episode; in none of the three patients who remained clinically stable did scrum samples show anti-HS reactivity. Anti-HS reactivity was only found in sera positive for anti-DNA by Farr assay but the anti-HS titre was not a mere reflection of the reactivity measured in the Farr assay. This indicates that only a subpopulation of anti-DNA can bind to HS. We found a high correlation (r=0.99) between anti-HS reactivities in plasma and serum and we conclude that anti-HS reactivity in scrum samples from SLE patients is not due to in vitro complex formation during clotting. Although further prospective analysis is necessary, our data suggest that measurement of anti-HS reactivity in SLE patients might identify patients at risk for the development of nephritis.
Patients with myasthenia gravis and thymoma have in their sera IgG autoantibodies against titin
Authors: AARLI J A , STEFANSSON K , MARTON L S G , WOLLMANN R L 
Published: July 2010

SUMMARYPatients with myasthenia gravis (MG) and thymoma have in their sera antibodies which react with non-receptor antigens from striated muscle. The purpose of this investigation was to characterize the antigen(s). Polypeptides in homogenates from rat skeletal muscle were separated by SDS-PAGE and trans-blotted to nitrocellulose. Sera from six patients with MG and thymoma stained a large (molecular weight &gt;500 kD) polypeptide. while no staining was observed with sera from 20 non-thymoma MG patients. Titin is one of the large (&gt; 500 kD) polypeptides of striated muscle and the antibody containing MG sera have antibodies that bind to titin in a preparation of myofibrillary proteins from rabbit skeletal muscle. The staining pattern is identical to that obtained with antiserum to titin, showing that the antigen has the same electrophoretic mobility as titin. Antibodies from the sera of the patients with MG and thymoma, affinity-purified on the large polypeptide, reacted with skeletal muscle sections in a cross-striational pattern, near the A/I band junction but within the I band, corresponding to the localization of one of the epitopes of titin. Our findings therefore indicate that the muscle antibodies found in the sera from some MG patients with thymoma are directed against titin.
Anti-mitochondrial antibodies (anti-M7) in heart diseases recognize epitopes on bacterial and mammalian sarcosine dehydrogenase
Authors: KLEIN R , BERG P A 
Published: July 2010

SUMMARYThe anti-mitochondrial antibody (AMA) anti-M7 has been shown to occur exclusively in sera from patients with acute and chronic myocarditis. Applying different enzymes of the inner mitochondrial membrane to ELISA, anti-M7-positive sera reacted only with sarcosine dehydrogenase (SD) from Pseudomonas aeruginosa. Testing these sera in the Western blot against a commercially available SD as well as against SD prepared from rat liver mitochondria, a determinant at 42 kD and 90 kD, respectively, was visualized. Using submitochondrial particles (SMP) from bovine heart and rat liver another major determinant at 64 kD could be observed with both antigen fractions. Liver SMP also expressed the SD-related, 90-kD epitope. Sera from patients with other AMA-positive and AMA-negative autoimmune diseases were negative with these different determinants. The identity of the 64-kD epitope on heart and liver SMP as well as the 42-kD polypeptide of bacterial SD and the 90-kD epitope on mammalian SD was proven by absorption studies and by elution of antibodies from the antigen bound to the immobilon sheets after immunoblotting. The SD enzyme activity was not affected by anti-64-kD and anti-42-kD antibodies in vitro. It is concluded that anti-M7 antibodies may be stimulated by an antigen expressed on cardiocytes during an infection which shares epitopes with SD, an evolutionary highly conserved protein. SD-sensitized B cell clones could therefore be triggered by the M7-antigen which shows homology to SD.
The expression of γΔ T cell receptor and the prevalence of primed, activated and IgA-bound T cells in Behçet's syndrome
Authors: FORTUNE F , WALKER J , LEHNER T 
Published: July 2010

SUMMARYMucosal ulceration of the oral, and to a lesser extent genital tissues is an essential feature of Behçet's syndrome and is associated with changes in the IgA class of immune responses. Indeed, a significant increase in the proportion of cytophilic IgAl was found in circulating CD8 and CD4 cells (P &lt; 0.01), with a corresponding decrease in IgA-Fc receptors on these T cells. Furthermore, 30–40% of the cytophilic IgA1 on T cells may have been of the polymeric secretory type and the rest of the monomeric variety. IgA isotype of B cells was also significantly increased (P &lt; 0.001), without an overall change in circulating B cells. However, a surprising finding was the significant up-regulation of γŞ T cell receptor in the CD8 (P &lt; 0.01) in the absence of a change in the proportion of αβ T cell receptor. The results suggest that some common microbial antigen might initiate at the mucosal surface an immune defence reaction characterized by T cells with γΔ receptors and IgA-specific B cells. However, IgAl bound to circulating T cells may down-regulate the central T cell function.
Terminally differentiated human intestinal B cells. J chain expression of IgA and IgG subclass-producing immunocytes in the distal ileum compared with mesenteric and peripheral lymph nodes
Authors: BJERKE K , BRANDTZAEG P 
Published: July 2010

SUMMARYTwo-colour immunofluorescencc staining for intracellular J chain and IgA (or J chain and IgG) was performed on tissue sections of normal human ileal mucosa (eight adult kidney donors), mesenteric lymph nodes (MLN), peripheral lymph nodes, and palatine tonsils. The most prominent J chain positivily was seen for IgA (97.3%) and IgG (81.7%) immunocytes in the ileal lamina propria (LP). Moreover, the proportion of J chain-expressing exlrafollicular immunocytes was significantly higher (P &lt; 0.05) in MLN than in peripheral lymph nodes for the IgA class (58.5%versus 25.6%); the same proportion for the IgG class was 45.9%versus 30.4%. In clinically normal palatine tonsils of adults, extrafollicular J chain expression was much lower than in peripheral lymph nodes; 14.2% for IgA cells and 5.5% for IgG cells. When related to subclass production, J chain expression was found to be higher for IgA2 than for IgA 1 cells in all tissues examined (palatine tonsils excluded because of a small number of lgA2 cells), the difference being significant in M LN and ileal LP (P &lt; 005). The J chain positivity tended to be higher for all IgG subclasses in MLN than in peripheral lymph nodes; this difference was significant (P &lt;005) for lgG2-producing immunocytes. Taking J chain expression as a marker of clonal immaturity, our results may reflect to some extent distribution of newly generated memory B cell clones from gut-associated lymphoid tissue to MLN. peripheral lymph nodes, and palatine tonsils in a strikingly decreasing order.
FK506, a novel immunosuppressive agent, induces antigen-specific immunotolerance in active Heymann's nephritis and in the autologous phase of Masugi nephritis
Authors: OKUBO Y , TSUKADA Y , MAEZAWA A , ONO K , YANO S , NARUSE T 
Published: July 2010

SummaryFK506 is a new drug which has potent immunosuppressive activity. We studied its immunosuppressive effects on active Heymann's nephritis and the aulologous phase of Masugi nephritis. The induction of active Heymann's nephritis was completely suppressed by FK506 injected simultaneously with the antigen (day 1) and then daily for 14 days at a dose of 0.64 mg/kg per day or more. With a lower dosage of this agent, antibody production and immune deposits in the glomerular basement membrane occurred despite the suppression of proteinuria. Similar results were obtained in rats on other treatment schedules (1–7 days or day 8–14 days duration). Rats that were prevented from developing Heymann's nephritis or the autologous phase of nephrotoxic antiserum nephritis by FK506 treatment exhibited a suppressed immune response to a second immunization of the same antigen even 4 weeks after cessation of drug administration; however, they developed antibodies when inoculated with other antigens. Rat peripheral leucocyte counts and scrum creatinin were not remarkably influenced by the administration of FK506. These results indicate that FK506 has potent immunosuppressive activity, and it is suggested that it is able to induce an antigen-specific immunotolerance.