Altered platelet magnesium and plasma and urinary soluble form of intercellular adhesion molecule I (sICAM-1) concentrations in insulin dependent diabetes mellitus (IDDM) patients with microalbuminuria

To examine the association between anticardiolipin (aCL) antibodies and epilepsy, we investigated the serum titers of aCL antibodies in a total 252 systemic lupus erythematosus (SLE) patients recruited in a prospective study. Twenty-one cases with epilepsy which were not attributable to any causes other than SLE were identified after being followed-up for five years. The clinical manifestations were recorded and blood samples were tested for the presence of aCL antibodies (IgG, IgM and IgA isotypes). Among 21 patients with epilepsy, 12 (57.1%), 2 (9.5%) and 2 (9.5%), respectively, had elevated baseline serum levels of IgG, IgM and IgA aCL antibodies. There was a dose-response relationship between risk of seizure and the baseline serum level of aCL antibodies (P < 0.01). The odds ratio of developing seizure were 3.7 for those who had a high level of aCL antibodies compared with those without a detectable level of aCL antibodies as the referent. Our results indicate that epilepsy as a primary neuropsychiatric event among lupus patients is associated with a high titer of aCL antibodies.     

Anticardiolipin antibodies and early infarct of the myocardium

The relationship between anticardiolipin antibodies (aCL) and acute myocardial infarction (AMI) is still controversial. The purpose of this study was to investigate the prevalence of aCL in young patients (age < or = 45 years) with AMI; record the aCL titre during different days of disease; assess the relationship between aCL titres and in-hospital myocardial infarction complications. The aCL were measured in 108 consecutive patients and in 31 controls (ELISA method). High aCL levels (IgG or IgM) were found in 19/108 (17.6%) patients and 5/31 (16.1%) controls (NS); aCL titres were similar in different days after AMI and did not differ in controls and in patients with or without early myocardial infarction complications. In conclusion, the aCL levels are not elevated in AMI patients, do not change during the early stage of the disease and are not associated with in-hospital complications.     

Detection of autoantibodies to the 90 kDa heat shock protein in systemic lupus erythematosus and other autoimmune diseases

Expression of the highly conserved 90 kDa heat shock protein (Hsp90) is elevated in the peripheral blood mononuclear cells of approximately 25% of patients with SLE. Conflicting data have been published about the frequency of antibodies to Hsp90 with the previous methodology using a complex Western blot system. We now describe an ELISA to measure autoantibodies to Hsp90 and Hsp70 in SLE patients, healthy controls and patients with a variety of autoimmune rheumatic diseases. IgG and IgM antibodies were elevated in 26 and 35% of SLE patients, respectively. These results show autoantibodies to Hsp90 (but not Hsp70) are elevated in a significant proportion of patients with SLE (P < 0.025) compared to healthy controls; and that those with raised antibody levels were more likely to have renal disease and a low C3 level (P < 0.02).     

Antibodies to beta2-glycoprotein I: a potential marker for clinical features of antiphospholipid antibody syndrome in patients with systemic lupus erythematosus

OBJECTIVE: To clarify risk factors for the development of clinical features of antiphospholipid syndrome (APS) in patients with anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE). METHODS: We studied 65 SLE patients, all with positive IgG and/or IgM aCL. Patients were divided into 2 groups; I: 29 SLE patients with features of APS (SLE/APS) and II: 36 aCL positive SLE patients without any feature of APS (SLE/aCL). Serum samples were collected from our serum bank. Anti-beta2-glycoprotein I (anti-beta2-GPI) were tested by ELISA using irradiated plates in the absence of cardiolipin. Anti-dsDNA antibodies were tested by standard Farr assay. RESULTS: There were no major differences between SLE clinical manifestations in both groups. However, the frequency of IgG anti-beta2-GPI was markedly increased in SLE/APS (18/29, 62%) than in SLE/aCL (4/36, 11%) (chi-squared 18.6, p=0.0001). The levels of anti-dsDNA antibodies in the same samples were slightly lower in SLE/APS. CONCLUSION: Our data suggest that increased levels of IgG anti-beta2-GPI may be a specific feature of SLE/APS patients rather than reflecting a polyclonal B cell activation.     

Antibodies to beta 2-glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus

OBJECTIVE: To investigate whether anticardiolipin antibodies (aCL) in patients with systemic lupus erythematosus (SLE) bind to beta 2-glycoprotein I (beta 2GPI), and to search for a relationship between the presence of IgG and/or IgM anti-beta 2GPI antibody and clinical manifestations in SLE patients. METHODS: IgG and IgM anti-beta 2GPI in 308 Japanese SLE patients were measured using phospholipid-independent enzyme immunoassays. Relationships to clinical histories and to various laboratory data were examined. RESULTS: The values of anti-beta 2GPI and aCL, as measured by conventional enzyme immunoassay, showed a strong correlation, but the anti-beta 2GPI assay was more useful in distinguishing beta 2GPI-dependent aCL from beta 2GPI-independent aCL. The presence of IgG anti-beta 2GPI was associated with an increased frequency of a history of thrombosis. Comparisons of various laboratory data suggested that the titer of anti-beta 2GPI may fluctuate with disease activity. CONCLUSION: The results suggest that pathogenic aCL is directed against structurally altered beta 2GPI and that enzyme immunoassay for anti-beta 2GPI may prove useful in evaluating the risk of thrombosis and monitoring the clinical course in patients with SLE.     

Platelet lactate dehydrogenase activity in systemic lupus erythematosus: correlation with anticardiolipin antibodies

OBJECTIVE: To evaluate lactate dehydrogenase (LDH) activity in platelet subpopulations in systemic lupus erythematosus (SLE) and to correlate platelet LDH activity with concentrations of anticardiolipin antibody (aCL). METHODS: Twelve female patients with SLE and 12 age matched female control subjects were studied. Platelets were separated on the Percoll gradient, their density values controlled by density marker beads. LDH activity was measured after platelet lysis, expressed as nU/fl. ELISA were used to measure levels of IgG and IgM aCL. RESULTS: A significant increase of LDH activity with a significant correlation to IgG and IgM aCL were found in small, light platelets with a volume < 5 mu 3 compared to large, dense platelets and to controls. LDH activity did not correlate with immunoglobulin classes, anti-DNA antibodies, and complement fractions in small and large SLE platelets. CONCLUSION: Our data suggest a possible chronic activation of subpopulations of small platelets in patients with SLE independent of thrombotic process. Low levels of aCL can mediate small platelet activation. Quantitative and qualitative analysis of the small, light platelets can serve a clinical diagnostic purpose as an in vivo platelet activation index in SLE.     

Detection of isotype-specific autoantibodies to calpastatin in sera from patients with rheumatic diseases using heat-treated HeLa cell extract as an antigen source for immunoblotting

To detect immunoglobulin isotype-specific autoantibodies to native human calpastatin in patients with rheumatic diseases, we performed immunoblot analysis using the heated HeLa cell extracts to enrich heat-resistant calpastatin. The calpastatin molecule that was apparently migrated to 110 kD by SDS-PAGE was confirmed to react with monoclonal anti-human calpastatin antibody in immunoblotting. IgG antibodies to calpastatin were detected in 22 of 48 sera (46%) from patients with RA, whereas only 20% (5/25), 11% (2/19) and 13% (2/15) of sera from SLE, SSc and PM/DM had IgG anti-calpastatin antibodies, respectively. IgM antibodies were also found in 40% (19/48) of RA and 12% (3/25) of SLE patients but not detected in sera from patients with other rheumatic diseases. IgA antibodies were found in only one RA and one SLE serum. In RA, 7 of 48 sera (15%) had IgM antibodies alone, but all SLE sera with IgM antibodies had IgG antibodies. Thus, anti-calpastatin autoantibodies were detected by using the native human calpastatin. Although these autoantibodies were found in patients with various rheumatic diseases, they were present in RA patients at the highest frequency. In particular, the presence of IgM antibodies appeared to be more specific in RA patients.     

Distinguishable patterns of connectivity in serum immunoglobulins from SLE patients and healthy individuals

Given that normal individuals maintain significant levels of serum autoantibodies that share many characteristics with those found in association with autoimmune diseases (AID), it has been proposed that disease could result from defects in supraclonal regulation, namely deviations of normal patterns of immunoglobulin (Ig) connectivity. Using conventional methods, together with a recently developed technique to quantitatively score a variety of V-region-dependent serum IgG interactions, the authors have now compared serum Ig connectivity in a group of patients with systemic lupus erythematosus (SLE) to healthy controls. The results demonstrate the existence of V-region interactions of serum IgG and IgM in SLE patients and healthy donors, with comparable connectivity titres, diversity and average affinities (microM range), but a wider individual variation and a tendency for higher F(ab')2 directed reactivities in the group of SLE patients. Multivariate statistics analysis of the data derived from reactivity patterns on F(ab')2 subsets, however, distinguished the two groups of donors, and demonstrated a larger dispersion and wider time-dependent variations in the patient population, as compared to healthy controls. The authors conclude that SLE is associated with circulating antibody repertoires that deviate from the patterns and levels of V-region connectivity characteristic of healthy individuals. These findings may shed light on the mechanisms of disease maintenance, and on the basis for the therapeutic effects of normal polyclonal Igs at high doses.     

Anticardiolipin antibodies in systemic lupus erythematosus: clinical correlates, HLA associations, and impact on survival

OBJECTIVE: To determine the frequency and clinical and HLA associations of anticardiolipin (aCL) antibodies in patients with systemic lupus erythematosus (SLE), as well as their impact on survival. METHODS: We studied 139 patients with SLE seen at a university based practice. We tested for clinical, laboratory, and HLA associations with levels of aCL antibody isotypes either in sera available in the bank (distant past) or in 2 samples. Demographic, clinical, laboratory, and HLA data were subjected to univariate survival analysis; variables of importance were entered into Cox multivariate regression analyses. RESULTS: aCL antibodies (any isotype) were present in 57 (41.0%) of the 139 patients tested in the distant past sample, and in 23 (32.3%) as a persistent event in the 71 patient subgroup tested twice. IgG aCL were significantly associated with deep venous thrombosis (DVT) (p = 0.04). No other clinical or HLA association was found with aCL positivity. In the survival analyses, older age at diagnosis, presence of major infections, endstage renal disease, and IgM aCL antibody positivity in the distant past emerged as important independent factors adversely affecting survival. In the subgroup tested twice for aCL antibodies (n = 71), persistent IgM aCL antibody positivity (n = 10) emerged as an important independent factor. Among the subgroup of patients that had HLA data available (n = 88), HLA-DQw7 and thromboembolic events also adversely affected survival. CONCLUSION: We confirmed the association of IgG aCL antibody positivity with DVT, and the impact on survival of endstage renal disease, major infections, and older age at diagnosis. IgM aCL antibody positivity present either as an isolated event in the distant past or as a persistent finding, thromboembolic events, and HLA-DQw7 emerged as important prognostic factors.     

Predictive value of Toxoplasma gondii antibody titres on the occurrence of toxoplasmic encephalitis in HIV-infected patients. ANRS 005/ACTG 154 Trial Group

OBJECTIVE: To study the predictive value of anti-Toxoplasma gondii antibody titres for the occurrence of toxoplasmic encephalitis (TE) in HIV-infected patients. METHODS: Data from the placebo arm of a trial of primary prophylaxis for TE (ANRS 005/ACTG 154) were analysed. Patients included had CD4+ cell counts < 200 x 10(6)/l and a positive Toxoplasma serology. Immunoglobulin (Ig) G and IgM Toxoplasma antibody titres at entry were retrospectively determined by enzyme-linked immunosorbent assay and agglutination on serum samples in a single laboratory. Incidence of TE was estimated by Kaplan-Meier method and a Cox model was used to study the predictive value of antibody titres, adjusted for other covariates. RESULTS: All 164 patients studied were positive for IgG antibodies and one had IgM antibodies. After a mean follow-up of 16 months, 31 cases of TE were documented. One-year incidence of TE was significantly higher in patients with IgG titres > or = 150 IU/ml (23.7%) than in patients with titres < 150 IU/ml (7.7%; relative risk, 3.1; P < 0.003). IgG titres remained significantly associated with the occurrence of TE (relative risk, 3.3; P < 0.005) in the Cox model. Predictive value of IgG titres did not differ according to baseline CD4+ cell counts. CONCLUSIONS: In patients with CD4+ cell counts < 200 x 10(6)/l, IgG anti-Toxoplasma antibody titre is a prognostic factor of occurrence of TE, with a higher risk for titres > or = 150 IU/ml. This finding should reinforce the recommendation of specific prophylaxis in these patients.     

Postoperative hepatic dysfunction in perspective. 1970

We measured the autoantibodies to GM1, central myelin proteins, and cardiolipin in 30 GBS patients using sensitive ELISA and Western blot techniques. The sequential modifications of titers during plasma-exchange (PE) and at follow-up were investigated in 15 patients. In pretreatment sera, we found significantly increased antibody titers to GM1 (37% of the patients), central myelin proteins (28%), and cardiolipin (21%). Seventeen patients out of 29 (58%) presented increased IgG or IgM antibody to at least one of the antigens considered as compared to 10 out of 70 controls (14%, P = 0.00001). By Western blot, IgG or IgM antibodies reactive with the triton insoluble fraction of central myelin were observed in 19 out of 28 GBS patients (67%). The follow-up measurements during and after PE showed a declining autoantibody titer in 10 out of 15 patients. However, in the remaining 5 GBS patients, we observed a persistently elevated titer or an increase from baseline values occurring during or after PE and reaching a peak. In 2 of the 5 patients, the titer peak preceded a clinical re-exacerbation. The presence of a persistently elevated or an increasing autoantibody titer during treatment with PE merits further investigation and may help to clarify the pathogenesis of GBS and improve its treatment.     

Association between antiphospholipid antibodies and arterial or venous thrombosis/thrombocytopenia

The relationship between thrombotic or thrombocytopenic complications and the existence of anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA) was studied in 146 patients with systemic lupus erythematosus (SLE). The prevalence of arterial thrombosis was obviously higher in patients who had both aCL and LA than in patients with either aCL or LA alone or in those with neither. Since a substantial fraction of the former group of patients with arterial thrombosis also had thrombocytopenia, there is a possibility that aCL and LA might enhance platelet activation and aggregation. To test this hypothesis, we studied the in vitro effects of aCL and LA on the enhancement of platelet activation by flow cytometric analysis using anti-CD62P and anti-CD41 monoclonal antibodies directed against platelet activation-dependent granule-external membrane (PADGEM) protein and platelet glycoprotein IIb (GPIIb). The IgG fraction purified from aCL+.LA+ plasma apparently enhanced platelet activation induced by adenosine diphosphate (ADP) at a low concentration, but IgG fractions from aCL+.LA- or aCL-.LA+ plasma did not cause enhancement of platelet activation. These results suggest that aCL and LA may cooperate to promote platelet activation, and may be involved, at least partially, in the pathogenesis of arterial thrombosis in patients with SLE.     

Procainamide-induced agranulocytosis differs serologically and clinically from procainamide-induced lupus

Agranulocytosis is a well recognized but uncommon complication of procainamide (PA) therapy, whereas a lupus-like syndrome occurs in approximately 20% of patients treated chronically with PA. In order to gain insight into the immunopathogenic relationships among these conditions, we compared the humoral immune abnormalities in these patient groups as well as in asymptomatic PA-treated patients. A relatively uniform profile of IgM but not IgG autoantibody reactivity with a set of chromatin-related antigens was observed in eight elderly men who developed agranulocytosis after treatment with PA. In contrast PA-induced lupus patients had predominant reactivity with [(H2A-H2B)-DNA] in both IgM and IgG classes. Five of eight patients with agranulocytosis had elevated levels of neutrophil-reactive IgG which appeared to be due to immune complexes based on Fc gamma receptor blocking studies. However, 12 of 15 patients with PA-induced lupus, none of whom had neutropenia, had similar levels of neutrophil-reactive IgG, suggesting that this reactivity was not causally related to agranulocytosis. Agranulocytosis developed after less than 3 months treatment with PA in six of eight patients. This time course was similar to that seen in 77 PA-induced agranulocytosis patients reported in the literature plus 127 patients reported to the U.S. Food and Drug Administration in whom 90% developed agranulocytosis within 3 months of starting PA. In contrast, the mode duration of treatment with PA before lupus-like symptoms develop is 10-12 months. These findings, together with the different profiles of autoantibodies and clinical presentations, suggest that agranulocytosis arises from a different mechanism than that underlying PA-induced lupus.     

Presence of anti-FKBP12 autoantibodies in patients with liver allografts: its association with allograft rejection

BACKGROUND: It was reported that autoantibodies against cyclophilin are present in sera from systemic lupus erythematosus. We hypothesized that autoantibodies against FKBP12, another immunophilin, may be present in the plasma of liver allograft recipients, which may affect the clinical outcome of liver allografts. METHODS: We investigated the relationship between the presence of anti-FKBP12 autoantibodies and rejection episodes in 47 patients treated with FK506 after living-related partial liver transplantation (LRLT). The patients consisted of two groups: 22 with rejection [R(+) group] and 25 without rejection [R(-) group]. The autoantibodies were measured by an indirect ELISA, and the specificity was confirmed by absorption with antigen and immunoblotting. RESULTS: The autoantibodies were detected in 13 of 22 in the R(+) group (IgG: 5; IgM: 6; both: 2) and in 6 of 25 in the R(-) group (IgG: 2; IgM: 3; both: 1) before LRLT (P=0.0193). After LRLT, they were also detected more frequently in the R(+) group (12 of 22; IgG: 1; IgM: 8; both: 3) than in the R(-) group (2 of 25; IgG: 1; IgM: 1) (P=0.001). In the R(+) group, the mortality of the patients who were positive and negative for the autoantibodies was 6 of 12 and 2 of 10, respectively. The autoantibodies were detected in all four patients with chronic or refractory acute rejection. The autoantibodies were not detected in any of the 34 healthy subjects. CONCLUSIONS: These results suggest that the presence of the autoantibodies in patients before transplantation is related to rejection, and the presence after transplantation may be associated with patient outcome.     

Cell-type specificity of anti-CD45 autoantibodies in systemic lupus erythematosus

OBJECTIVE: To determine the specificity of anti-CD45 autoantibodies in systemic lupus erythematosus (SLE) for native CD45 and for CD45 expressed by T cells and B cells, and at different stages of cellular activation. METHODS: CD45 purified from different types of lymphocytes was examined by immunoblotting with sera from patients with SLE. Indirect immunofluorescence experiments were performed with purified anti-CD45 autoantibodies. RESULTS: IgM anti-CD45 autoantibodies in SLE recognize native CD45 expressed on the surface membrane of viable lymphocytes and CD45 purified from activated peripheral T cells and certain T cell lines, but not CD45 purified from B cells or resting peripheral T cells. The presence or absence of reactivity is independent of the individual isoforms expressed. CONCLUSION: Recognition of CD45 by IgM antilymphocyte autoantibodies in SLE varies with the lineage and state of activation of the lymphocyte target. This pattern of reactivity is consistent with autoantibody specificities involving CD45 glycoforms, rather than CD45 isoforms.     

Anticardiolipin antibodies are associated with pulmonary hypertension in patients with mixed connective tissue disease or systemic lupus erythematosus

Anticardiolipin antibodies (aCL) were studied in relation to pulmonary hypertension (PH) in 22 patients with mixed connective tissue disease (MCTD) or systemic lupus erythematosus (SLE). The mean pulmonary arterial pressure (mPAP) values were similar in the 12 MCTD and 10 SLE patients: 26 +/- 11 and 25 +/- 11 mm Hg, respectively. However, the frequency of PH was higher in SLE (60%) than in MCTD patients (33%). The titers of aCL were significantly higher in SLE (38 +/- 27 IU/ml) than in MCTD (17 +/- 7 IU/ml; p < 0.02). Two SLE patients with high titers of aCL had multiple cerebral infarction and transverse myelitis, and deep vein thrombosis, respectively. A significant correlation between the titers of aCL and mPAP was observed in patients with MCTD (p < 0.05), but not in patients with SLE.     

Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis

The aim of this study was to determine whether latent viral infection is associated with idiopathic pulmonary fibrosis (IPF), an interstitial lung disease whose aetiology remains to be elucidated. Cytomegalovirus (CMV) immunoglobulin G (IgG) and complement fixation (CF), Epstein-Barr (EB) viral capsid antigen (VCA) IgG, herpes simplex virus (HSV) IgG, adenovirus CF, and parainfluenza 3 virus haemagglutinin inhibition (HI) titres were measured in the serum from patients with pulmonary diseases. The study included five subject groups: 35 normal controls (aged (mean +/- SD) 38 +/- 17 yrs); 43 IPF (63 +/- 10 yrs), seven collagen vascular disease-related interstitial pneumonitis (CVD-IP) (62 +/- 12 yrs); 22 sarcoidosis (36 +/- 14 yrs); and 17 emphysema (66 +/- 11 yrs). Levels of CMV IgG in IPF (87.6 +/- 51.7) and CVD-IP (101.2 +/- 69.9) were significantly elevated compared to those in the control (30.9 +/- 24.1), sarcoidosis (34.4 +/- 38.3) and emphysema groups (40.3 +/- 24.6), whereas CMV immunoglobulin M (IgM) was generally below the limit of detection. Similarly, CMV CF titres in IPF and CVD-IP were elevated compared to those in other diseases. EB VCA IgG titres in IPF, CVD-IP and emphysema and HSV IgG in IPF were also elevated. In contrast, adenovirus CF and parainfluenza 3 HI titres demonstrated no significant difference among all of the groups investigated. Increases in cytomegalovirus immunoglobulin G and complement fixation titres with negative cytomegalovirus immunoglobulin M suggest that latent cytomegalovirus infection may be more prominent in idiopathic pulmonary fibrosis or collagen vascular disease-related interstitial pneumonitis. Together with the elevation of Epstein-Barr virus viral capsid antigen and herpes simplex virus immunoglobulin G in idiopathic pulmonary fibrosis and/or collagen vascular disease-related interstitial pneumonitis, it is rational to assume that these viruses may be implicated in the development of pulmonary fibrosis. Further study is necessary to investigate the relationship between latent viral infection and pulmonary fibrosis.     

Immunological liver diseases in children

Pristane induces a lupus-like syndrome characterized by autoantibody production and glomerulonephritis in nonautoimmune strains of mice. Although it has been suggested that this syndrome results from nonspecific immune activation, there is little evidence so far that B cells are activated nonspecifically by pristane or that this promotes autoimmunity. In this study, we examined whether polyclonal hypergammaglobulinemia occurs in pristane-induced lupus, and its relationship to the production of anti-DNA, nRNP/Sm, and Su autoantibodies. In conventionally housed mice, there was a marked increase in total IgM and IgG3 2 weeks after i.p. pristane injection, followed by increased IgG1, IgG2a, and IgG2b levels. IgM levels were higher in pristane-treated specific pathogen-free (SPF) mice than in conventionally housed mice, whereas IgG and IgA levels were reduced. Pristane induced anti-nRNP/Sm and Su autoantibodies in SPF mice, but their onset was delayed and levels were lower than those in conventionally housed mice. There was no consistent relationship between total IgG1, 2a, and 2b hypergammaglobulinemia and production of anti-nRNP/Sm and Su autoantibodies. Moreover, the total Ig levels were similar in the anti-nRNP/Sm-positive and -negative groups. In contrast, production of IgM anti-ssDNA antibodies paralleled IgM hypergammaglobulinemia in some, but not all, mice. These studies indicate that pristane-induced lupus is associated with marked hypergammaglobulinemia, the magnitude of which is influenced by the microbial environment. However, anti-nRNP/Sm and Su autoantibody production is at least partly independent of polyclonal B cell activation. The data strongly suggest that pristane-induced lupus is not exclusively the consequence of nonspecific immune stimulation. They also point to the importance of microbial stimulation in the development of hypergammaglobulinemia in this inducible lupus model.     

Occurrence of anti-C1q antibodies in IgA nephropathy

BACKGROUND: The pathogenic mechanisms and the antigens involved in the establishment and progress of IgA nephropathy are unknown. As antibodies against C1q have been reported to correlate with SLE nephritis, we analysed the occurrence of these antibodies in IgA nephropathy in order to investigate the possibility of pathogenetic similarities in these renal disorders. METHODS: The occurrence of IgA- and IgG anti-C1q antibodies (anti-C1q) were determined by ELISA in patients with IgA nephropathy (n = 36) and SLE nephritis (n = 37), diseases both known to be associated with circulating immune complexes. Levels of these antibodies were also determined in two other glomerular diseases, i.e. idiopathic membranous glomerulonephritis (n = 7) and minimal change disease (n = 2), in which circulating immune complexes are usually not present, and in 40 healthy controls. RESULTS: IgA anti-C1q was observed in increased titres in 11/36 of the patients with IgA nephropathy, in 2/37 of the patients with SLE nephritis (both with proliferative disease) and in 1/9 of the patients with membranous and minimal change disease (P < 0.001). Increased titres of IgG anti-C1q were observed in 1/36 of the patients with IgA nephropathy, in 17/37 of the patients with SLE nephritis and in 0/9 of the patients with membranous and minimal change disease (P < 0.001). There were no correlations between the levels of anti-C1q antibodies and clinical parameters such as degree of proteinuria, haematuria, or renal function. Nor was there any correlation to the concentration of C3a and the terminal complement complex (TCC) in patients with IgA nephropathy. CONCLUSIONS: The occurrence of anti-C1q antibodies in both IgA nephropathy and SLE nephritis, albeit of different predominating isotypes, indicates the possibility of a similar pathogenic mechanism involved in these renal disorders. The occurrence of IgA anti-C1q antibodies in patients with IgA nephropathy has to our knowledge not previously been reported.     

Self-reactive B cells in nonautoimmune and autoimmune mice

The defining feature of autoimmune disease is the presence of specific autoreactive lymphocytes. Systemic lupus erythematosus (SLE), for example, is characterized by a discrete set of antibodies directed to nuclear antigens; these include autoantibodies to DNA and snRNPs that are diagnostic for SLE. The murine model of SLE, the MRL-lpr/lpr mouse, likewise, has a similar autoantibody profile. To understand how SLE-associated autoantibodies are regulated in healthy individuals and to identify mechanisms underlying their expression in autoimmunity, we have developed a transgenic (tg) model system using multiple sets of tgs. The development of B cells bearing these tgs has been studied in BALB/c and MRL-lpr/lpr autoimmune backgrounds, and the relative fates of anti-ssDNA and anti-dsDNA tg B cells when they are a part of a diverse as well as monoclonal B cell repertoire have been evaluated.