bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequence Analysis and Idiotypic Relationships of BEG-2, a Human Fetal Antibody Reactive with DNA
Authors: Watts R.A. , Hillson J.L. , Oppliger I.R. , Mackenzie L. , Lydyard P.M. , Mackworth Young C.G. , Brown C. , Staines N.A. , Isenberg D.A.
Published: November 2007

Monoclonal antibody (mAb) BEG-2 is a dsDNA binding IgM λ derived from a 12-week human fetus. Two binding site idiotypes (BEG-2 Id α and BEG-2 Id β) have been defined with the use of polyclonal rabbit anti-idiotypic anti-serum. BEG-2 Id α is located on the λ light chain and has been described previously. The BEG-2 Id β is present on the μ heavy chain. By means of a direct binding ELISA, BEG-2 Id β has been identified on EBV-derived mAbs from human fetal liver or spleen (5%), human cord blood (2.7%) and adult peripheral blood (1%). In addition, the Id is present on 8.5% of adult spleen-derived hybridoma antibodies and 6% of RA synovium-derived hybridoma antibodies. In all populations the presence of the Id is associated with binding to DNA and other polyanions. Competition indicated that the Id was located at or near the antigen-binding site on these molecules. To explore the structural basis of this binding, a major part of the BEG-2 chain was sequenced and found to be encoded by a member of the VH4 family joined to a variant of JH5 by a very short Diversity or N region. Of the BEG-2 Id β positive mAbs for which the VH family has been determined, five are encoded by VH4 and two are encoded by VH6, but none is encoded by other families. Thus, the BEG-2 Id β identifies a set of polyreactive antibodies that are common in fetal life, into adulthood and are encoded by VH6 and, a subset of VH4 genes.
Spontaneous Activation of Transforming Growth Factor-β Gene Transcription in Broncho-Alveolar Mononuclear Cells of Individuals with Systemic Autoimmune Diseases with Lung Involvement
Authors: Deguchi Y. , Kishimoto S.
Published: November 2007

The spontaneous elevation of the transcription of the transforming growth factor-β (TGF-β) gene in broncho-alveolar mononuclear cells (BMC) of individuals with autoimmune diseases with lung involvement, by nuclear run-on transcription assay, is shown in this study. In quantification analysis of TGF-β gene transcription, we found more than 10 times the enhanced transcription of the TGF-β gene in BMC of individuals with autoimmune diseases with involvement, in comparison to normal healthy subjects or patients with bronchial asthma used as controls. Our observation suggests that TGF-β, a potent mitogen for fibroblasts, may be produced in BMC during an active immune response in individuals with systemic autoimmune diseases with lung involvement, and may be involved in autoimmune-related pathophysiological changes of cytokine networks in lung involvement such as lung fibrosis.
Short Course of Weekly Low-Dose Intravenous Pulse Cyclophosphamide in the Treatment of Lupus Nephritis: A Preliminary Study
Authors: Houssiau F.A. , D'Cruz D.P. , Haga H.-J. , Hughes G.R.V.
Published: November 2007

We review our experience with low-dose intravenous pulse cyclophosphamide as treatment of biopsy-proven lupus nephritis. Seventeen patients were treated with 2-4 (mostly 3) weekly low-dose intravenous pulses of cyclophosphamide (500 mg) and moderate doses of prednisolone (0.5mg/kg/day), followed by an oral immunosuppressive drug (either azathioprine or cyclophosphamide). As compared with the classical monthly high-dose cyclophosphamide regimen, this weekly low-dose regimen induced neutropenia in one patient only. The incidence of herpes zoster was very low (6 %). At the end of the follow-up period (15 ± 8 months), two patients required chronic ambulatory peritoneal dialysis. The 14 patients that could be evaluated improved their mean serum albumin from 30 ± 7 to 37.5 ±7 g/l (mean ± SD; P < 0.01) and their mean serum creatinine fell from 125 ± 119 to 101 ± 66 μmol/l (not significant). Mean DNA binding dropped from 71 ± 29 to 26 ± 27 % (P < 0.001) and mean complement fraction C4 levels increased from 14 ± 8 to 28 ± 18 mg/dl (P < 0.05). The mean daily prednisolone dose was dramatically reduced from 26 ± 8 to 10 ± 4 mg (P < 0.001). Although this preliminary and retrospective study clearly needs validation with a larger cohort followed for a longer period, it seems that a treatment combining moderate doses of steroids and 3-4 weekly low-dose intravenous pulses of cyclophosphamide, followed by oral immunosuppression, is well tolerated and beneficial — at least in the short term — for most patients with severe lupus nephritis.
Autoimmunity, Polyclonal B-Cell Activation and Infection
Authors: Granholm Norman A. , Cavallo Tito
Published: November 2007

It is widely believed that autoimmunity is an integral part of the immune system, and that genetic, immunologic, hormonal, environmental and other factors contribute to the pathogenesis of autoimmune disease. Thus, autoimmune disease may represent an abnormal expression of immune functions instead of loss of tolerance to self, and it can be organ specific or systemic in its manifestations. We review the various factors that contribute to the development of autoimmune disease; we also review the mechanisms of polyclonal B-cell activation, with emphasis on the role of infectious agents. We consider systemic lupus erythematosus in humans and in experimental animals as prototypic autoimmune disease, and we summarize data to indicate that polyclonal B-cell activation is central to the pathogenesis of systemic autoimmune disease. The effect of polyclonal B-cell activation, brought about by injections of a B-cell activator - lipopolysaccharide from Gram-negative bacteria—is sufficient to cause autoimmune disease in an immunologically normal host. In fact, autoimmune disease can be arrested if excessive polyclonal B-cell activation is suppressed; alternatively, autoimmune disease can be exacerbated if polyclonal B-cell activation is enhanced. We explore the mechanism of tissue injury when autoimmune disease is induced or exacerbated, and we consider the pathogenic roles of autoantibodies, immune complexes, complement, the blood cell carrier system, and the mononuclear phagocyte system. Although polyclonal B-cell activation may be the mechanism whereby various factors can cause or exacerbate systemic autoimmune disease, polyclonal B-cell activation may cause autoimmune disease on its own.
Antiphospholipid Antibodies Differ in aPL Cofactor Requirement
Authors: Sammaritano Lisa R. , Lockshin Michael D. , Gharavi Azzudin E.
Published: November 2007

Although autoimmune antiphospholipid antibodies (aPL) may require a serum cofactor, beta2-glycoprotein I (β2GPI), for maximal binding in aPL ELISA, it is not known whether cofactor is absolutely required or is merely an enhancing factor for binding, nor is it clear whether aPL bind to cofactor itself, a cofactor-lipid complex, or a phospholipid modified in some way by cofactor. We therefore isolated and purified β2GPI and evaluated its relationship to both IgG and IgM aPL binding. aPL derived from different sera appear to have differing requirements for cofactor; the proportion of total binding attributable to cofactor varies from 46% to 95%. aPL do not bind to β 2GPI in the absence of phospholipid. Enhanced binding to phospholipid is seen if β2GPI is provided either before or with the test antibody. Autoimmune aPL bind phospholipid better with human rather than bovine cofactor. The requirement for cofactor is greater for low-avidity aPL as measured in an IgG-human cofactor system. Cofactor requirement alone does not predict the presence or absence of associated clinical complications.
Distribution of Two Common Idiotypes of Anticardiolipin Antibodies in Sera of Patients with Primary Antiphospholipid Syndrome, Systemic Lupus Erythematosus and Monoclonal Gammopathies
Authors: Krause I. , Cohen J. , Blank M. , Bakimer R. , Cartman A. , Hohmann A. , Valesini G. , Asherson R.A. , Khamashta M.A. , Hughes G.R.V. , Shoenfeld Y.
Published: November 2007

The frequency of two common idiotypes of anticardiolipin antibodies (aCL) was determined in sera from three groups of subjects, patients with systemic lupus erythematosus (SLE), with primary antiphospholipid syndrome (PAPS) and with monoclonal gammopathies (MG), as compared to normal population.

The idiotype 1.10, which was derived from a patient with active SLE and antiphospholipid syndrome, was found more frequently among patients with PAPS (10.5%, 10.5% and 22.20% in MG, SLE and PAPS, respectively) than the idiotype H3, which was derived from a human hybridoma monoclonal aCL generated from a healthy subject immunized with tetanus and diphtheria. The latter idiotype was detected in 8.7%, 6.5% and 11.7% of patients with MG, SLE and PAPS, respectively. Incidental findings in this study include a high prevalence of aCL among patients with MG (23%) and a high prevalence of anti-dsDNA antibodies, detected only by a sensitive enzyme-linked immunosorbent assay, among patients with PAPS. Our results indicate that idiotypic diversity exists among aCL derived from different sources. Some of these cross-reactive idiotypes may be more pathogenic than others.
Impaired Urinary Excretion of Soluble IL-2 Receptors in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis
Authors: Manoussakis M.N. , Germanidis G.S. , Drosos A.A. , Moutsopoulos H.M.
Published: November 2007

Several previous studies have demonstrated increased in vivo release of soluble interleukin-2 receptors (sIL-2R) in patients with disorders associated with cellular activation. In this study attempting to understand better the role of sIL-2R released in vivo, we investigated the sIL-2R levels in paired serum and urine samples from 25 patients with systemic lupus erythematosus (SLE), 41 patients with rheumatoid arthritis (RA) and 20 healthy subjects. Using an ELISA for sIL-2R, we detected significantly increased urinary sIL-2R levels in normal individuals (868 ±114 units/ml) compared to the corresponding serum samples (209 ± 25, P < 0.001, mean urine/serum sIL-2R ratio: 4.5 ± 0.6), which suggests that the clearance of sIL-2R from circulation is largely kidney-dependent.

The patients with SLE and RA exhibited significantly increased serum sIL-2R levels compared to normals (682 ± 115 and 734 ± 101 units/ml, respectively, P < 0.001) and these levels correlated with disease activity. However, urinary excretion of sIL-2R in these patients (SLE: 620 ±154 units/ml; RA: 1084 ± 148 units/ml) was found to be significantly decreased (mean urine/serum sIL-2R ratio in SLE: 0.9 ± 0.2; in RA: 1.9 ± 0.2; P < 0.001) compared to normals, possibly contributing to the accumulation of these soluble receptors in the serum of autoimmune patients after their release from cells. Our findings can be attributed either to the binding of the sIL-2R to serum protein(s) or to distinct structural features of serum sIL-2R in SLE and RA patients, interfering with the urinary excretion of these molecules.
Small Nuclear Ribonucleoprotein Particles Contain Glycoproteins Recognized by Rheumatic Disease-Associated Autoantibodies
Authors: Jintao Chen  , Agris Paul F.
Published: November 2007

Proteins from U1 and U2 small nuclear ribonucleoprotein (snRNP) particles, which are common targets of autoantibodies found in some rheumatic diseases, were analysed for the presence of glycans. A glycan detection assay revealed that the U1-specific proteins 68K and A and the U2-specific protein B" are glycosylated. However, none of the Sm proteins, which are common to all the major snRNP particles, showed a detectable level of glycosylation. With the use of specific lectins, an analysis of the particular carbohydrate(s) attached to the U1 snRNP 68K protein demonstrated the presence of at least one N-linked oligosaccharide chain. Lectin detection of galactose, glucose, mannose and N-acetylglucosamine on 68K was confirmed by chemical analysis of the carbohydrates. The glycopeptide nature of these antigens may be important for understanding the role of autoantigens in the pathogenesis of autoimmune disorder.
Prevalence of Non-Organ-Specific Autoantibodies in Pregnant and Non-Pregnant Healthy Women
Authors: Mavridis Anestis K. , Liu Xue Ming  , Hatzipetrou Peter , Lentzaris Gregory , Papanikolaou Nicolas G. , Tzioufas Athanasios G. , Moutsopoulos Haralampos M.
Published: November 2007

The prevalence of autoantibodies during pregnancy was studied. Sera from 568 women (203 pregnant and 365 non-pregnant) were tested for autoantibodies to double-stranded DNA, car diolipin and extractable cellular antigens. Nineteen out of 203 pregnant women (9.4%) had at least one autoantibody against double-stranded DNA or cardiolipin, mainly of the IgM class. The non-pregnant control group had significantly higher incidence of autoantibodies (17.8%; X2 = 7.39, P < 0.01). Sixty-six out of 568 women had had spontaneous abortions in their past medical history, but there was no correlation between them and the presence of anticardiolipin antibodies. Two of the non-pregnant women had anti-Ro(SSA) antibodies. These findings suggest that (a) the prevalence of autoantibodies decreases during pregnancy; and (b) the presence of anticardiolipin antibodies in healthy pregnant women does not cor relate with any pregnancy-related complications. However, our results indicated that auto immunity is a rather common disorder in healthy women.
Serum Apolipoprotein H Levels in Systemic Lupus Erythematosus Are Not Influenced by Antiphospholipid Antibodies
Authors: Ichikawa Yukinobu , Takamatsu Kazunaga , Shimizu Hiroaki , Uchiyama Mitsuaki , Moriuchi Junko , Takaya Masatoshi , Kobayashi Nobumasa , Kawada Tsutomu , Arimori Shigeru
Published: November 2007

Anticardiolipin antibodies (aCL) were recently discovered to recognize a complex consisting of phospholipids and apolipoprotein H (apo H). In this study, we determined the serum apo H levels in 36 systemic lupus erythematosus (SLE) patients with or without antiphospholipid antibodies (aPL), including aCL and lupus anticoagulants, to clarify the possible effects of aPL on apo H levels in vivo.

The apo H levels were low in SLE patients as compared with 22 healthy controls. However, no associations were found between apo H levels and circulating aPL or clinical features of the antiphospholipid antibody syndrome. A secondary hyperlipidemic state, which probably related to lupus nephritis (proteinuria) and/or prednisolone treatment, increased apo H levels in SLE patients.
Antigen-Binding Diversity of Human Hybridoma Autoantibodies Derived from Splenocytes of Patients with SLE
Authors: Ravirajan C.T. , Kalsi J. , Winska Wiloch H. , Barakat S. , Tuaillon N. , Irvine W. , Cockayne A. , Harris A. , Williams D.G. , Williams W. , Axford J. , Muller S. , Isenberg D.A.
Published: November 2007

The antigen-binding specificity of human hybridoma-derived monoclonal autoantibodies (mAb) was analysed with mAbs derived from the spleens of two patients with active systemic lupus erythematosus (SLE). From one patient 72 mAbs (RSP clones) and from the other 173 mAbs (RT clones) were obtained. The binding specificity of these mAbs was analysed by solid- and fluid-phase ELISA against the autoantigens ssDNA, dsDNA, cardiolipin, SmRNP, histones, Sm-D and SS-B (La) synthetic peptides, and foreign antigens including bacterial polysaccharides. In addition, antinuclear antibody activity and anti-dsDNA binding were con firmed by fluorescence staining methods. Reflecting the patient's serological profile, none of the antibodies from the RSP clones reacted with ssDNA or dsDNA but 12 reacted with car diolipin. In addition, three mAbs reacted with H4, five with U 1 RNP, two with Sm-D peptides and 12 with SS-B peptides. In contrast, from the RT fusion, nine mAbs reacted with ssDNA, HI and SS-B peptides, seven with cardiolipin, four with dsDNA, two with Sm-D peptides and one each with H2A, H3 and H4. In many cases one mAb showed reactivity with more than one antigen: for example, mAb RT 72 binds to ssDNA, dsDNA, cardiolipin, H1, H4 and an Sm-D peptide; RT 6 binds to H1, SmRNP and ubiquitinated histone H2A. However, none of the antibodies showed 'across the board' polyreactivity; indeed, the selectivity of the reactions was notable and marked variation in antibody affinity was recorded. Eight of the mAbs bound to Salmonella typhimurium and two to the Klebsiella polysaccharide K-30. This report con firms the diversity in the antigen-binding pattern and polyreactivity of autoantibodies derived from SLE patients and supports the notion that antibodies to autoantigens can also bind to foreign antigens. It also suggests that the antigen-binding profiles of human hybridoma- derived antibodies reflect the range of antibodies present in the serum of individual patients.
DNA Binding to Mouse Cells is Mediated by Cell-Surface Molecules: The Role of These DNA-Binding Molecules as Target Antigens in Murine Lupus
Authors: Hefeneider Steven H. , McCoy Sharon L. , Morton Jane I. , Bakke Antony C. , Cornell Kenneth A. , Brown Lisa E. , Bennett Robert M.
Published: November 2007

Autoimmunity to a 28-29-kDa cell-surface DNA-binding molecule has previously been described in patients with systemic lupus erythematosus and related autoimmune diseases. This report describes experiments that implicate a similar antigen-antibody system in the evolution of autoimmunity in lupus-prone mice. DNA binding to murine spleen cells was found to be a saturable phenomenon that was inhibited by excess cold DNA and trypsinization. The role of autoimmunity to murine cell-surface DNA-binding molecules in lupus-prone mice (MRL lpr/lpr, MRL + / +, BXSB) was compared to normal mice (BALB/c, C3H.SW) by means of an assay that measured the inhibition of cell-surface DNA binding. Only sera from lupus strains had inhibitory activity and this component was shown to be an IgM autoantibody. Furthermore, we isolated a spontaneously occurring IgM monoclonal antibody from the spleen of an MRL/lpr mouse, which inhibited DNA binding to mouse cells. Time-course studies indicated that young female MRL/lpr mice lacked detectable activity against cell- surface DNA-binding molecules; however, by 8-10 weeks maximal inhibitory activity was observed. This response occurred prior to the development of significant antinuclear antibody activity. With the appearance of overt disease and anti-DNA antibodies, inhibition of DNA- binding activity became undetectable. These findings mirror previous studies on autoimmunity to a cell-surface DNA-binding molecule on human leucocytes, but have the added advantage of permitting the study of the temporal evolution of this inhibitory activity in relation to disease expression.
Review: Multiorgan Thrombotic Disorders in Systemic Lupus Erythematosus: A Common Link?
Authors: Asherson Ronald A. , Cervepa Ricard , Font Josep
Published: November 2007

Multiorgan thrombotic disorders have been described in a variety of conditions including systemic lupus erythematosus. Among these are the 'catastrophic' antiphospholipid syndrome, disseminated intravascular coagulation and the thrombotic thrombocytopenic purpura-haemolytic uraemic syndrome. In this review we briefly analyse some specific clinical and haematological characteristics of these conditions and attempt to uncover common links between them.
Can Experienced Clinicians Predict the Outcome of Lupus Nephritis?
Authors: Esdaile John M. , Mackenzie Todd , Barré Paul , Danoff Deborah , Kirk Osterland C. , Somerville Peter , Quintal Hélène , Kashgarian Michael , Suissa Samy
Published: November 2007

The ability of four experienced clinicians to predict short-term outcome (serum creatinine level at 1 year) and long-term outcome (renal insufficiency) was evaluated in 87 patients with lupus nephritis. The correlational agreement and the accuracy of their predictions were contrasted with the actual outcomes observed and with statistically generated prognostic regression models.

In contrast to previously published data, all four clinicians predicted both short-term outcomes (P < 0.001) and long-term outcomes (P < 0.02) well. The clinicians' predictions approximated that of a statistically generated computer model for both agreement and accuracy for renal function at 1 year. The four clinicians identified nearly identical clinical variables as important in determining prognosis. Provision of biopsy data to the clinicians improved short-term and long-term prediction slightly.

The value of the statistical models was 'validated' by demonstrating that three of the four clinical variables identified by the models, but not by the clinicians, could enhance clinical prediction (P < 0.05). In addition, the extent of tubulo-interstitial involvement on biopsy, a predictor that has recently received increased attention, could improve the long-term clinical predictions of all four clinicians (P < 0.05).
I-123 Iofetamine SPECT Scan in Systemic Lupus Erythematosus Patients with Cognitive and Other Minor Neuropsychiatric Symptoms: A Pilot Study
Authors: Rogers Malcolm P. , Waterhouse Elizabeth , Nagel James S. , Roberts Neal W. , Stern Steven H. , Fraser Patricia , Partridge Robert , Murawski Benjamin , Khoshbin Shahram , Holman B. Leonard , Schur Peter H. , Liang Matthew H.
Published: November 2007

Accurate diagnosis of central nervous system (CNS) lupus remains difficult, especially when the manifestations are of subtle cognitive and affective changes. This pilot study reports on the use of I-123 iofetamine single photon emission computerized tomography (SPECT) scans in 18 such patients with documented systemic lupus erythematosus. Eight of the 18 scans were abnormal (44%), four in a diffuse bitemporo-parietal pattern previously noted only in Alzheimer's disease, and four with large focal deficits. Neither the existence of the abnormal scan nor the particular pattern of abnormality correlated with the results of other diagnostic tests. These preliminary results raise the possibility that SPECT scans may offer an additional valuable diagnostic instrument in CNS lupus, although further studies are necessary to delineate their precise role.
Prevalence of Acne Rosacea in a Rheumatic Skin Disease Subspecialty Clinic
Authors: Black Alison Adams , McCauliffe Daniel P. , Sontheimer Richard D.
Published: November 2007

There are many causes of malar erythema besides the classic butterfly rash of acute cutaneous lupus erythematosus (LE). Twenty-one patients (6.7% of new patient visits) referred to a dermatology department-based rheumatic skin disease subspecialty clinic over a 5-year period in whom a diagnosis of cutaneous LE had been entertained were found to have diagnoses other than autoimmune connective tissue diseases. Sixteen of the patients in this cohort (76%) had acne rosacea (rosacea), while the remaining five had other dermatologic disorders. Review of their records revealed that upon referral nine of these 21 patients (43%) had positive antinuclear antibody (ANA) assays, most with insignificant or marginal titers by our laboratory standards. On repeat ANA testing in our laboratory, all of these patients had insignificant ANA titers. Physicians may be giving too much weight to low-titer ANAs in assessing patients with isolated malar erythema. These issues are discussed in the overall context of the differential diagnosis of malar erythema. A simple punch skin biopsy can be very helpful in distinguishing cutaneous LE from other causes of malar erythema.
Bacterial Lipopolysaccharide Causes Variable of Diverse Immunoglobulin Isotypes in Kidneys of Lupus-Prone Mice
Authors: Granholm Norman A. , Cavallo Tito
Published: November 2007

We investigated the role of immunoglobulin isotypes in the exacerbation of lupus nephritis associated with exposure to bacterial lipopolysaccharide. The data indicate that enhanced polyclonal B-cell activation and exacerbated autoimmune disease evoked by lipopolysaccharide are associated with an increase in the concentration of isotypes in plasma and in renal eluate, that this isotype response is polyclonal and preferential but not restrictive, that all B cells are responsive but all are not equally sensitive to the effects of lipopolysaccharide, and that some expanded isotypes may be more nephritogenic in certain strains of lupus-prone mice.
Prevalence of Anticardiolipin Antibodies in Subacute Cutaneous Lupus Erythematosus
Authors: Fonseca E. , Alvarez R. , Gonzalez M.R. , Pascual D.
Published: November 2007

We examined the prevalence of the antibodies to cardiolipin measured by solid-phase enzyme immunoassay during a prospective study of patients with subacute cutaneous lupus erythematosus (SCLE). Seven of 44 (16%) consecutive patients with SCLE had positive anticardiolipin antibodies; of these only three satisfied the American Rheumatism Association's revised criteria for the classification of systemic lupus erythematosus.

Clinical findings probably associated with the positive anticardiolipin antibodies were found in four cases, including clotting abnormalities, thrombocytopenia, hemolytic anemia, livedo reticularis, chilblain lupus erythematosus lesions, migraine, leg venous thrombosis and pulmonary embolism after surgery, and spontaneous abortion.

Our data suggest that it is reasonable to screen SCLE patients for these antibodies to confirm the presence of the antiphospholipid syndrome.
Review: Complement and Lupus: Old Concepts and New Directions
Authors: Porcel Jose Manuel , Vergani Diego
Published: November 2007

In this review it is our intention to outline briefly the relevance of the complement system in systemic lupus erythematosus. Three main issues will be addressed: the role of complement in handling immune complexes (ICs), the association between complement deficiencies and IC diseases, and the value of measuring complement components and their conversion products in monitoring disease activity.
Lupus-Derived Human Monoclonal IgM anti-DNA Antibody Displays Monospecificity, High Affinity and Private Idiotype Specificity
Authors: Suenaga Ronsuke , Abdou Nabih I.
Published: November 2007

A human monoclonal IgM k anti-DNA antibody, designated 2F7, was prepared by somatic hybridization of peripheral blood lymphocytes from a lupus patient with a human-mouse heterohybridoma cell line, K6H6/B5. 2F7 was tested for its antigen binding and idiotypic specificity by direct binding and inhibition enzyme-linked immunosorbent assays. 2F7 had a high binding activity to single-stranded DNA (ssDNA) but not to double-stranded DNA. It cross-reacted with single-stranded homopolymers with pyrimidine bases and double-stranded polynucleotides containing those homopolymers, suggesting that 2F7 recognizes a conformational determinant made up of both deoxyribose-phosphate backbone and specific nucleotide base. 2F7 did not cross-react with eight structurally unrelated self-antigens. Dissociation constant (Kd) of 2F7 for sonicated ssDNA was approximately 4.5 × 10 -9 M, indicating its relatively high affinity. Idiotypic characterization with rabbit anti-idiotype raised against 2F7 suggested that 2F7 expressed an idiotype at or near its antigen-binding sites that was not detected in sera from 20 unrelated lupus patients, 10 lupus family members and 10 normal individuals. These results suggest that certain IgM class anti-DNA antibodies in human systemic lupus erythematosus may arise by antigen stimulation and not simply by polyclonal B-cell activation.
The Clinical Significance of Measuring Different Anti-dsDNA Antibodies by Using the Farr Assay, an Enzyme Immunoassay and a Crithidia luciliae Immunofluorescence Test
Authors: Werle Egon , Blazek Marta , Fiehn Walter
Published: November 2007

Anti-double-stranded DNA (dsDNA) antibodies are highly specific for the diagnosis of systemic lupus erythematosus (SLE) but are heterogeneous in respect to, for example, avidity, class and cross-reactivity. Sera from 2061 patients were measured by three methods: an enzyme-linked immunosorbent assay (ELISA), an indirect immunofluorescence test with Crithidia luciliae as substrate (CLIF), and the Farr assay, a radioimmunological method based on the ammonium sulfate precipitation of immune complexes. The different anti-dsDNA antibody determinations were evaluated by analysis of patient records. The reason for a reactive Farr assay in 14 patients was predominantly the measurement of antibodies of the IgM class, which are not detected by the ELISA. The detection of additional antibodies to dsDNA of the IgA class, to single-stranded DNA or to histones plays a minor role. In comparison with the Farr assay, we found more positive results with the ELISA, which additionally detects anti-dsDNA antibodies of low avidity. The ELISA might also yield positive values in conditions such as chronic liver diseases, various infections and connective tissue diseases other than SLE. Avoiding the disadvantages of radioactivity, the ELISA is well suited as a screening test for dsDNA antibodies. However, positive results should be confirmed by the CLIF test or preferably by the Farr assay, thus combining sensitivity with specificity.
IgG Subclasses in Systemic Lupus Erythematosus and Other Autoimmune Rheumatic Diseases
Authors: Blanco F. , Kalsi J. , Ravirajan C.T. , Speight P. , Bradwell A.R. , Isenberg D.A.
Published: November 2007

In this study the concentration of the different subclasses of IgG in sera from patients with a range of autoimmune rheumatic diseases (ARD) was detected by radial immunodiffusion. In the second part the IgG subclasses of autoantibodies that recognize single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), Ro, La, Sm and RNP in patients with ARD were measured by enzyme-linked immunosorbent assay.

We studied 15 patients with lupus, 20 patients each with primary and secondary Sjögren's syndrome (SS) and 10 each with rheumatoid arthritis (RA), scleroderma and myositis. Twenty healthy controls were also measured.

The serum concentration of IgG2 in ARD patients was generally reduced. In contrast, the concentrations of IgG1, IgG3 and IgG4 subclasses were normal or raised. A high degree of correspondence in the IgG1, IgG2 and IgG3 responses to dsDNA and ssDNA in SLE was found. Notable differences in the IgG1 anti-Ro and ssDNA responses compared to the other subclasses were seen in 1° and 2° SS. In addition, an unexpected high level of IgG4 antibodies to ssDNA in 1° SS (65%) and IgG4 antibodies to Sm/RNP in RA was observed.
The Clinical Significance of Autoantibody Profiles in Patients with Systemic Lupus Erythematosus
Authors: Thompson Darren , Juby Angela , Davis Paul
Published: November 2007

We have evaluated the autoantibody profiles in the sera of 117 patients with systemic lupus erythematosus (SLE) and compared and contrasted the clinical and laboratory features of the disease of patients segregated according to an autoantibody profile. Using this approach we are able to demonstrate that autoantibody profiles identified subsets of patients with SLE. Patients with a negative autoantibody profile had fewer clinical and laboratory features of their disease when compared to the other subsets of patients. In contrast, patients with profile A (anti-nDNA and/or anti-Sm antibodies) had a statistically significant increase in malar rash, renal and hematologic involvement and hypocomplementemia when compared to patients with a negative profile. Patients with profile B (anti-nRNP antibodies) had a clinical pattern of disease different from that of patients with profile A and had a statistically significant increase in Raynaud's phenomenon when compared to patients with a negative profile. Patients with profile C (anti-SSA and/or anti-SSB antibodies) had a statistically significant increase in lupus-related rashes and photosensitivity. None of the lupus patients reviewed in this study had profile D (antibodies to centromere and/or Scl-70), this profile being seen largely in patients with scleroderma or one of its variants. Both patients with profile E (antihistone antibodies) had drug-induced lupus.

We conclude that the use of autoantibody profiles defines subsets of patients with lupus that may have clinical, therapeutic and prognostic implications.
Warts and Lupus Erythematosus
Authors: Yell J.A. , Burge S.M.
Published: November 2007

The human papilloma virus is implicated in causing several diseases, ranging from the common wart to malignancy. We describe a high prevalence of cutaneous warts in lupus erythematosus. The presence of warts did not correlate with the taking of immunosuppressive drugs. This observation suggests that there is a primary immunological defect among patients with lupus erythematosus. We found this high rate among patients with discoid as well as systemic lupus erythematosus. We found no correlation between the prevalence of cutaneous warts and cervical dysplasia, or malignancy. Discoid lupus erythematosus is often considered to be a different disease from systemic lupus erythematosus, running a more benign course. The high prevalence of cutaneous warts in both conditions highlights yet another similarity between these two diseases.
Autoimmune Thyroid Disorders in SLE in Singapore
Authors: Boey M.L. , Fong P.H. , Lee J.S.C. , Ng W.Y. , Thai A.C.
Published: November 2007

One hundred and twenty-nine patients with systemic lupus erythematosus were screened for thyroid function tests. Of these, 8.9% had hyperthyroidism and 3.9% Hashimoto's thyroiditis. Euthyroid sick syndrome was present in 47.8% of patients. There was a high prevalence of antimicrosomal and antithyroglobulin antibodies (32.2%). Abberations in thyroid function tests are common in SLE but the incidence of thyroid failure is low.
Salmonella Infection in Systemic Lupus Erythematosus
Authors: Shahram Farhad , Akbarian Mahmood , Davatchi Fereydoun
Published: November 2007

Patients with systemic lupus erythematosus (SLE) are susceptible to infections, notably salmonellosis. We report 37 cases of salmonella infection in 24 patients with SLE. These cases were detected in a group of 770 patients with SLE. All the patients were women, with a mean age of 25.6 years. At the onset of salmonella infection, 81 % were taking prednisolone and 27 % were taking cytotoxic drugs. Renal involvement was present in 75% of patients, which was approximately the same as in other SLE patients. Bacteremia, arthritis, osteomyelitis and rare manifestations of salmonellosis, including pulmonary and urinary tract involvement, were encountered. Diagnosis was based on isolation of the microorganism, mostly from blood cultures. Salmonella species other than typhi and paratyphi were often responsible. Widal agglutination test was positive in less than half the cases, and leukopenia was not seen frequently. Recurrence of infection in 29% of the patients and the high mortality rate (28.5%), despite the conventional period of appropriate antimicrobial treatment, show a poor prognosis of salmonellosis in SLE patients. This special picture of salmonellosis argues for a much longer period of treatment in these patients.
Fibrin Deposition in SLE Glomerulonephritis
Authors: Mccutcheon J. , Evans B. , D'Cruz D.P. , Hughes G.R.V. , Davies D.R.
Published: November 2007

Coagulation and fibrinolytic processes are involved in the pathogenesis of some forms of glomerulonephritis. In human renal disease extensive fibrin deposition is mainly associated with severe diseases such as rapidly progressive glomerulonephritis. Staining methods for fibrin have problems and many immunohistochemical methods do not distinguish fibrinogen from fibrin and its degradation products, which result from coagulation. The presence of cross-linked fibrin in the glomerulus indicates that coagulation has occurred, but the presence of fibrinogen may be a result of non-specific protein permeation. A monoclonal antibody (DD3B6) has been used to demonstrate cross-linked fibrin in 30 renal biopsies in systemic lupus erythematosus. The biopsies were also stained with an 'antifibrinogen' and an antiplatelet antibody. The severity of renal disease in each biopsy was graded by both the World Health Organization (WHO) classification and Austin's Activity and Chronicity Indices. Three of the renal biopsies were shown to stain with DD3B6 and five stained with antiplatelet antibody. Twenty-seven contained fibrinogen and there was no evidence of intraglaynerular coagulation in these biopsies.

The biopsies containing cross-linked fibrin were all in WHO group IVc. The severity of disease measured by Austin's Activity Index was no greater in these biopsies than in other biopsies in WHO Group IVc in which cross-linked fibrin was not detected.

The presence of cross-linked fibrin may be associated with intraglomerular coagulation and more severe disease.
Clinical Profile of Chinese Patients with Systemic Lupus Erythematosus
Authors: Lee S.S. , Li C.S. , Li P.C.K.
Published: November 2007

In the 9-year period between 1982 and 1991, 137 patients attending a medical clinic of Queen Elizabeth Hospital, Hong Kong, were diagnosed as having systemic lupus erythematosus according to the American Rheumatism Association's criteria for classification. The female-to-male ratio was 16 to 1. Commonly the onset age was between 20 and 40. Malar rash (70%), arthritis (70.8%) and nephropathy (69.3%) were the most common manifestations. Antinuclear factor was invariably positive, whereas anti-extractable nuclear antigen antibodies were positive in varying degrees—Sm 12.7%, nRNP 28.8%, Ro 60.2%, La 8.4%. There were 22 deaths during the follow-up period, two-thirds from active diseases. Gastro-intestinal bleeding and opportunistic infection were common complications.
Anti-Intrinsic Factor Antibodies in Systemic Lupus Erythematosus
Authors: Junca Jordi , Cuxart Alfons , Olive Alejandro , Tural Cristina
Published: November 2007

As the co-existence of pernicious anaemia (PA) and systemic lupus erythematosus (SLE) has been repeatedly reported, we have investigated the presence of anti-intrinsic factor antibodies (IFAb), the immunological hallmark of PA, in patients diagnosed with SLE. Serum cobalamin levels and IFAb were determined in 30 women diagnosed with SLE as well as in 45 controls. Cobalamin levels were low in 7/30 patients. IFAb were detected in 3/30 sera from patients but in none of the control sera. The presence of IFAb was associated with a low cobalamin concentration, anaemia and macrocytosis in only one patient. There was no evident relationship between the presence of IFAb and serological markers of SLE. We conclude that IFAb may appear in SLE patients, although the cobalamin deficiency described in SLE seems to be due to the presence of IFAb in only a minority of cases.
Prevalence of Systemic Lupus Erythematosus in India
Authors: Malaviya A.N. , Singh R.R. , Singh Y.N. , Kapoor S.K. , Kumar A.
Published: November 2007

Prevalence of systemic lupus erythematosus (SLE) was studied in the northern Indian population by means of a two-pronged approach: (a) antinuclear antibody (ANA) screening of the general population by a new well-standardized finger-prick 'filter paper' technique (sensitivity and specificity: 95.4% and 86.2%, respectively); and (b) a questionnaire survey carried out primarily by trained personnel in the community (sensitivity and specificity: 100% and 68.6% respectively).

The low specificity of the two methods was improved by the introduction of a step of secondary screening by the authors, thus excluding false positives. ANA screening of 52 062 individuals yielded 13 positive results, of which only two were found to be true cases of SLE after secondary screening. Questionnaire survey of 39 826 individuals similarly yielded 3393 positive results. On secondary screening, only one of these persons was found to be a case of SLE. Thus, three cases of SLE were detected in a population survey of 91 888, giving a point prevalence of 3.2 per 100 000 (95% CI = 0-6.86 per 100 000). The reported prevalence of SLE ranges from 14 to 60 per 100 000. Thus, the prevalence of SLE in India is comparatively low. Although the reasons for low prevalence are not clear, the study used highly sensitive methodology and it is therefore unlikely that SLE cases were missed. It is hypothesized that SLE is a disease of modernization and therefore its prevalence in a predominantly rural population like that of India is low.
Amyotrophic Lateral Sclerosis in a Patient ivith Systemic Lupus Erythematosus
Authors: Forns Xavier , Bosch Xavier , Graus Francesc , Navarro Margarita , Font Josep
Published: November 2007

We report the case of a 48-year-old woman diagnosed as having systemic lupus erythematosus who developed a neurological disorder that finally resulted in amyotrophic lateral sclerosis. Although neurological disturbances caused by systemic lupus erythematosus are protean, there are no reported cases of amyotrophic lateral sclerosis associating with lupus disease. This association and the suspected autoimmune mechanism of pathogenesis in amyotrophic lateral sclerosis suggest that this might not be a simple coincidence but perhaps a causal relationship.
Effect of Procainamide and Hydralazine on Poly (ADP-ribosylation) in Cell Lines
Authors: Ayer Linda M. , Edworthy Steven M. , Fritzler Marvin J.
Published: November 2007

The prescription drugs procainamide (PA) and hydralazine (HYD) are associated with the induction of autoimmunity and a clinical syndrome called drug-induced lupus. Since PA- and HYD-induced autoantibodies are directed primarily against histones and histones are prime acceptors of poly (ADP-ribose) (PADPR), we have investigated the effects of PA and HYD on the activity of poly (ADP-ribose) polymerase (PADPRP). Control substances, with structures similar to PA and HYD but not known to induce lupus, included N-acetylprocainamide (NAPA) and the amino acids phenylalanine, tryptophan and proline, and their amide derivatives. Wil-2 cells were incubated in 0.5-50 μM PA, NAPA and HYD, which included therapeutic concentrations of these drugs. The mean enhancement of incorporation of [3H]-nicotinamide adenine dinucleotide (NAD) into PADPR was 1.84 (P = 0.005) with PA, with HYD 1.48 (P = 0.029), and with NAPA 1.38 (P = 0.036). This increase was suppressed by 3-aminobenzamide, an inhibitor of PADPRP activity. Little or no increase in [3H]-NAD incorporation was observed with equivalent concentrations of phenylalanine, phenylalaninamide or tryptophan. However, a 1.29-fold increase was noted with 0.5 μM tryptophanamide, a 1.26-fold increase with 0.5 μM prolinamide and a 1.4-fold increase with 50 μM proline. PA increased PADPRP activity in B- and T-cell lines but not in promyelocytic leukemia or epithelial cell lines. Since poly (ADP-ribosylation) is important in the cellular response to various agents, the increased ADP-ribosylation of intracellular molecules may be a key event in the induction of autoantibodies.
Drug-Induced Systemic Lupus Erythematosus in a Nine-Year-Old Boy
Authors: Ansell Barbara M.
Published: November 2007

After a series of intercurrent infections, a 9-year-old boy on ethosuximide for petit mal developed typical drug-induced systemic lupus erythematosus. After ethosuximide was stopped, he continued to deteriorate and was treated with corticosteroid therapy, which could be only gradually tapered off over many months. Follow-up 4 years later showed him to be completely well.
Blood Transfusion Related HBV and HIV Infection in a Patient with SLE
Authors: Bambery Pradeep , Deodhar Shridhar D. , Malhotra Harinder S. , Sehgal Shobha
Published: November 2007

We described the course of a young man with SLE who developed hepatitis B virus and human immunodeficiency virus infections through contaminated blood tranfusion. He presented with severe SLE, improved on treatment and then developed hepatic failure which responded to conservative treatment. He now has AIDS and the SLE and HBV infection are quiescent.
Review: Role of Transforming Growth Factor Beta (TGFβ) in Systemic Autoimmunity
Authors: Del Giudice Gina , Crow Mary K.
Published: November 2007

Transforming growth factor (TGFβ) is a multifunctional cytokine with proinflammatory as well as immunosuppressive activities. A regulatory role for TGFβ has been suggested in investigations of several experimental and spontaneous models of pathological autoreactivity. It is suggested that many of the functional effects of TGFβ parallel the major immune system abnormalities seen in SLE.
Effects of an Aromatase Inhibitor on Thymus and Kidney and on Oestrogen Receptors in Female MRL/MP-lpr/lpr Mice
Authors: Greenstein B.D. , Dhaher Y.Y. , Bridges E. de F. , Keser G. , Khamashta M.A. , Etherington J. , Greenstein A.S. , Coates P.J. , Hall P.A. , Hughes G.R.V.
Published: November 2007

The effects of an aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA), which blocks oestrogen formation, have been studied in female MRL/MP- lpr/lpr mice which are a model of SLE. At 11.5 weeks, mice were implanted subcutaneously either with empty Silastic implants or with implants containing 25 mg 4-OHA. At 15 weeks, they were sacrificed by decapitation and liver, thymus, kidneys and uterus taken for wet weight, histology and measurement of cytosolic and nuclear oestrogen receptors. Thymus weights were significantly lower in 4-OHA-treated mice although uterus weights were similar in both groups. Also, whereas thymuses from control-treated mice were packed with plasma cells with abundant cytoplasm, those from 4-OHA-treated mice contained T cells with large nuclei. Relative oestrogen receptor abundances were: uterus > liver > thymus, although cytosolic receptors could not be detected in thymus cytosols of MRL mice unless they were treated with the aromatase inhibitor. In kidney, there was histological evidence that inflammation was limited to mesangium in 4-OHA-treated mice. These results support the hypothesis that oestrogens may be involved in the aetiology of murine SLE and provide data suggesting that substances which block oestrogen production in vivo may be useful to treat certain forms of SLE.
Effect of Sex on the Induction of Anti-DNA Antibodies in Normal Mice Immunized with Bacterial DNA
Authors: Palmer Scott M. , Gilkeson Gary S. , Pisetsky David S.
Published: November 2007

Immunization of normal mice with bacterial DNA elicits a significant IgG anti-DNA response and has been explored as a model of systemic lupus erythematosus. To determine whether this induced response is influenced by sex, we have measured anti-DNA levels in normal male and female BALB/c mice immunized with single stranded DNA from E. coli as complexes with methylated bovine serum albumin (mBSA) in adjuvant. By ELISA assays, anti-DNA levels of immunized females were approximately 16-fold higher than those of immunized males; levels of antibodies to the mBSA carrier were similar, however. The antibodies from females and males showed a similar degree of cross-reactivity when assayed using other natural and synthetic DNA antigens, including mammalian DNA. These findings suggest the potentiation of anti-DNA production in females by antigen-specific mechanisms and provide further evidence that immunization with bacterial DNA replicates features of autoantibody production in SLE.
Pericardial Complication of Neuropsychiatric Systemic Lupus Erythematosus
Authors: Sarkar David , Taylor J.L. , Hoffbrand B.I.
Published: November 2007

A 28-year-old woman presenting with systemic lupus erythematosus stuck two sewing needles into her pericardium while psychotic from cerebral lupus. We believe this is a unique cause of acute pericarditis as a complication of SLE.
Elevated Levels of the 70 kD Heat Shock Protein in Patients with Systemic Lupus Erythematosus are not Dependent on Enhanced Transcription of the hsp70 Gene
Authors: Twomey Breda M. , Amin Vaksha , Isenberg David A. , Latchman David S.
Published: November 2007

The level of the heat inducible hsp70 protein (hsp72) has been shown to be elevated in the peripheral blood mononuclear cells of a subset of SLE patients. We show that this increased level of hsp70 is not dependent on enhanced transcription of the hsp70 gene or elevated levels of the hsp70 mRNA, neither of which are observed in SLE patients with enhanced protein levels. This indicates that post-transcriptional processes involving either improved translatability of the hsp70 mRNA or increased protein stability are responsible for the observed increase in protein levels in these patients.