Raised serum IgG and IgA antibodies to mycobacterial antigens in rheumatoid arthritis.

Autoantigens cross reactive with mycobacteria are implicated in the pathogenesis of adjuvant arthritis in the rat, and there are reports of changes in the immune response to mycobacteria in human rheumatoid arthritis (RA). We have therefore examined the IgM, IgG, and IgA antibody levels to crude mycobacterial antigens and to two recombinant mycobacterial heat shock/stress proteins (65 kD and 71 kD) in sera from patients with RA, systemic lupus erythematosus (SLE), and Crohn's disease, and from healthy controls. IgA binding to the crude mycobacterial antigens was significantly raised in RA sera, though IgG and IgM binding tended to be lower than in controls. Both IgA and IgG binding to the heat shock proteins were significantly raised in the RA sera. Smaller significant rises in both classes were seen in sera from patients with SLE, and in the IgA class only to the 65 kD protein in Crohn's disease. The rises in IgG and IgA antibodies to the 65 kD protein in RA were significantly higher than in the other diseases, however. It is interesting that this protein is the one responsible for adjuvant arthritis in the rat.     

Antiphospholipid antibodies: clinical significance in systemic lupus erythematosus

A radioimmunoassay using cardiolipin as antigen and labelled SPA, anti-human IgG, anti-human IgM, anti-human IgA as second antibodies in detecting anti-cardiolipin antibody with the sera from 308 patients and 70 normal controls. Among them, 126 patients were of SLE, 27 systemic sclerosis, 40 rheumatoid arthritis, 40 Sj?gren syndrome, 26 other connective tissue diseases, 7 syphilis and 32 with obstetric complications. The positive rate of anticardiolipin antibody were 42.9% (SLE), 29.7% (PSS), 20% (RA), 15% (SS), 26.9% (CTD), 85.7% (syphilis), 3.1% (obstetric complication), 0% (NC). In SLE the anticardiolipin antibody were well correlated with thrombocytopenia, cerebral lupus, thrombosis of vein and spontaneous recurrent abortion. Lupus anticoagulant (APTT) was found in 21.3% of SLE and biological false positive of VDRL test in 4.8%. Both of them correlated with the anticardiolipin antibody detected by the radioimmunoassay. The authors concluded that antiphospholipid antibodies is a group of commonly seen antibodies, which may play a rule in the pathogenesis of SLE. Further study is progressing.     

Differences in immunochemical characteristics of cryoglobulins in rheumatoid arthritis and systemic lupus erythematosus and their complement binding properties.

Cryoglobulins isolated from sera of patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were analysed for their immunoglobulin, antibody, and complement components. In both disease categories the cryoglobulins contained predominantly IgG with lesser amounts of IgM and IgA, but relative to serum more IgM was concentrated in the cryoglobulins. IgM rheumatoid factor was found in 65% of RA cryoglobulins but in only 17% of SLE cryoglobulins (p less than 0.02), whereas SLE cryoglobulins contained more DNA binding activity than RA cryoglobulins (p less than 0.01). C1q binding activity was detectable in the majority of SLE and RA sera and SLE cryoglobulins. Paradoxically only two out of 34 RA cryoglobulins bound C1q, although rheumatoid factor activity was present in both cryoglobulins and sera. When isolated from serum the rheumatoid factor fraction strongly bound C1q. Both RA and SLE cryoglobulins contained similar small amounts of C3 and C4. Differences in antibody composition and complement binding activity of cryoglobulins from RA and SLE sera may reflect properties of immune complexes which affect their tissue localisation and pathogenicity.     

Isotypes of anti-beta2-glycoprotein I antibodies: association with thrombosis in patients with systemic lupus erythematosus

OBJECTIVE: To evaluate the association between isotypes of anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) and thrombosis and to identify antiphospholipid antibodies (aPL) that are most associated with thrombosis in patients with systemic lupus erythematosus (SLE). METHODS: IgG anticardiolipin antibody (aCL) and isotypes of anti-beta2-GPI were measured by ELISA, and clinical evidence of thrombosis was analyzed in 270 patients with SLE. RESULTS: IgG, IgM, and IgA anti-beta2-GPI were positive in 38.1, 13.7, and 34.8% of patients, respectively. Patients with a history of thrombosis were significantly more likely to have lupus anticoagulant (LAC), IgG aCL, and the 3 anti-beta2-GPI isotypes. Arterial thrombosis was associated with the presence of IgG aCL and the 3 anti-beta2-GPI isotypes, whereas venous thrombosis was associated with LAC, IgG aCL, and IgA anti-beta2-GPI. In stepwise multivariate logistic regression analysis, the variable that was associated with thrombosis was IgA anti-beta2-GPI. The occurrence of arterial thrombosis was associated with IgG aCL and that of venous thrombosis was related to IgA anti-beta2-GPI in stepwise multivariate analysis. The IgG, IgM, and IgA anti-beta2-GPI titers were closely correlated with IgG aCL titers. The IgA anti-beta2-GPI titers were also significantly correlated with those of IgG and IgM anti-beta2-GPI. CONCLUSION: The results suggest that anti-beta2-GPI isotypes are related to the occurrence of thrombosis, and measurements of IgA anti-beta2-GPI may be useful for predicting thrombotic episodes in patients with SLE.     

The Detection of Immune Complexes of Different Immunoglobulin Class

Summary: Immune complexes were detected in 51 sera from patients with a variety of immunological diseases: 14 systemic lupus erythematosus (SLE); 14 infectious mononucleosis (IM); 12 rheumatoid arthritis (RA) and 11 subacute bacterial endocarditis (SBE). Three methods were used to detect complexes: the fluid—phase Clq binding assay (Clq.BA); the solid—phase Clq binding assay (Clq.SP) and the Raji cell radio-immunoassay (RIA). Modification of the Clq.SP and the Raji cell RIA by use of monospecific antisera to immunoglobulins G, A and M enabled the class of antibody in the immune complexes to be determined. Antibodies of all three classes were found in each disease, the predominant ones being IgG and IgM in SLE and SBE, IgM and IgA in RA and IgM in IM.     

Demonstration and differentiation of circulating immune complexes in chronic inflammatory rheumatic diseases using a semiautomated PEG-precipitation laser nephelometer test

Circulating immune complexes were determined in rheumatoid arthritis and systemic lupus erythematosus using a semiautomated PEG-precipitation laser-nephelometer technique. Immunoglobulins IgA, IgG and IgM as well as complement proteins C3c and C4 were quantitatively determined in 2.75% PEG-precipitates. The PEG-precipitates obtained from the sera of healthy controls, SLE patients, and RA subjects displayed different protein patterns. In RA sera a significant elevation of all investigated proteins was found. In SLE sera, a significant increase of IgG, IgA, IgM, and C3 was found, whereas C4 was significantly reduced as compared to the controls. Typical values for a calculated IgG/C4 ratio in circulating immune complexes were obtained for RA and SLE. In RA this ratio remained unchanged in different activity stages and was found in seropositive as well as in seronegative sera. Thus circulating immune complexes from SLE and RA sera differ with respect to the degree of complement-dependent solubilization.     

Ro/SSA and La/SSB specific IgA autoantibodies in serum of patients with Sjögren's syndrome and systemic lupus erythematosus

OBJECTIVE: To investigate the occurrence of IgA autoantibodies to Ro 52 kDa, Ro 60 kDa and La antigen in serum of patients with primary Sj?gren's syndrome (pSS) and systemic lupus erythematosus (SLE). METHODS: Recombinant Ro 52 kDa, Ro 60 kDa and La antigens were used to analyse autoantibodies in serum from 25 patients with pSS, 30 patients with SLE and 20 controls using a semiquantitative immunoblotting approach. RESULTS: Among the patients with pSS, 21 (84%) had detectable IgA autoantibodies to Ro 52 kDa, 13 (52%) to Ro 60 kDa and 20 (80%) to La antigen. The corresponding results for the patients with SLE were 22 (73%), 14 (47%) and 20 (67%), respectively. No IgA autoantibodies against the three antigens were detected in 20 normal controls. A comparison of several clinical features with the titres of IgA antibodies to Ro 52 kDa, Ro 60 kDa and La, revealed a significant relation between IgA anti-Ro 52 and IgA anti-La to sicca (p< 0.05). Semiquantitative data suggest that IgG is the dominating antibody to the three antigens followed by IgM > IgA in both SLE and pSS patients. Specificity studies of IgA autoantibodies with different subfragments of Ro 52 kDa and Ro 60 kDa antigens showed that IgA antibodies did not differ from IgG and IgM in their recognition pattern. CONCLUSION: These results suggest that besides IgM and IgG, IgA autoantibodies are also detected at high frequency in patients with pSS and SLE. Further studies are necessary to evaluate the contribution of these IgA autoantibodies to inflammation as well as their diagnostic value.     

IgG, IgA, IgM antibodies to a viral citrullinated peptide in patients affected by rheumatoid arthritis, chronic arthritides and connective tissue disorders

OBJECTIVES: Anti-citrullinated protein/peptide antibodies (ACPA), a family of antibodies with overlapping specificities, represent a specific marker of rheumatoid arthritis (RA). The aim of the present study is to investigate the prevalence and clinical significance of IgG, IgA and IgM ACPA by a newly described assay employing a viral citrullinated peptide (VCP). METHODS: IgG, IgA and IgM anti-VCP antibodies have been measured in sera from 146 patients affected by RA and 404 controls, including 204 chronic arthritides, 111 connective tissue disorders and 89 healthy subjects. The affinity of the different isotypes for VCP was analysed by liquid phase inhibition assays. RESULTS: Among RA patients, 40 were single positive for IgG anti-VCP, five for IgA and 11 for IgM. Ten patients were double positive for IgG and IgA, four for IgG and IgM, six for IgA and IgM. In 15 RA patients IgG, IgA and IgM anti-VCP antibodies were detected. No correlation could be found between the isotype and the clinical manifestations or duration of the disease. IgA anti-VCP were strongly associated with RA, whereas IgM anti-VCP were detected also in a low percentage of systemic lupus erythematosus, psoriatic arthritis and mixed cryoglobulinaemia (MC) patients. IgG anti-VCP displayed a higher affinity for the antigen than IgA or IgM. CONCLUSIONS: These data show that anti-VCP of IgG and IgA isotype discriminate RA from other chronic arthritides and disease controls and suggest an independent production of each isotype.     

IgA and IgG autoantibodies against alpha-fodrin as markers for Sjögren's syndrome. Systemic lupus erythematosus

OBJECTIVE: To determine the prevalence of IgA and IgG autoantibodies against alpha-fodrin in patients with primary and secondary Sj?gren's syndrome (SS) and controls. METHODS: An ELISA detecting IgA and IgG antibodies against alpha-fodrin was developed. We examined the prevalence of IgA and IgG antibodies against alpha-fodrin in patients with primary and secondary SS, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) and blood donors. RESULTS: IgA antibodies against alpha-fodrin were detected in 64% of patients with primary SS (n = 85), 47% of patients with secondary SS and SLE (n = 15), and 86% of patients with secondary SS and RA (n = 7). IgA autoantibodies against alpha-fodrin were detected in only one of 160 sera obtained from blood donors and in one of 50 and 2 of 12 sera obtained from SLE and RA patients without sicca syndrome, respectively. The prevalence of IgG antibodies against alpha-fodrin in SS was lower: they were detected in 55% of sera obtained from patients with primary SS, 40% of patients with secondary SS and SLE, and in 43% of patients with secondary SS and RA. Three of 160 sera from blood donors and one of 50 and 5 of 12 sera from SLE and RA patients without sicca syndrome, respectively, contained IgG antibodies against alpha-fodrin. CONCLUSION: IgA rather than IgG antibodies against alpha-fodrin are specific for and frequently observed in primary and secondary SS and are useful markers for this autoimmune disorder.     

Anti-Clq antibodies in patients with chronic hepatitis C infection

OBJECTIVE: Extrahepatic autoimmune features of HCV infection include autoantibody production and the development of mixed cryoglobulinemia. Anti-Clq antibody, detected with high frequency in systemic lupus erythematosus and hypocomplementemic urticarial vasculitis, may have a direct pathogenic role in complement mediated autoimmune diseases. In this study, we investigate the prevalence of anti-Clq antibody in a population of patients with chronic HCV infection. METHODS: Serum was obtained from a group of 50 patients with chronic HCV infection and control groups comprised of patients with SLE, rheumatoid arthritis (RA), scleroderma (PSS), Sj?gren's syndrome (SS), mixed connective tissue disease (MCTD), and healthy individuals. RESULTS: Anti-Clq antibody was detected in 38% of HCV patients compared with 2% of healthy controls (p < 0.0001). Levels were also significantly elevated in patients with SLE (61%), RA (20%), PSS (15%), SS (15%) and MCTD (15%). CONCLUSION: In addition to numerous other autoantibodies, patients with chronic HCV infection exhibit increased production of anti-Clq IgG antibodies. This observation may have implications for the pathogenesis of the mixed cryoglobulinemic vasculitis syndrome.     

Clinical significance of anti-dsDNA antibody isotypes: IgG/IgM ratio of anti-dsDNA antibodies as a prognostic marker for lupus nephritis

The objective of this paper is to investigate the association between patterns of anti-dsDNA antibody isotypes and specific clinical manifestations (categorized in renal, musculoskeletal, cutaneous, hematological, pulmonary, neurological and cardiac). Sera of 202 systemic lupus erythematosus (SLE) patients, 33 patients suffering from other autoimmune diseases and 115 healthy blood donors were analysed for anti-dsDNA antibodies by IgG-, IgA- and IgM-specific ELISA, Farr-assay and CLIF. A subset of 24 SLE patients was investigated in a longitudinal study over a period of one to six years. Disease activity of 105 SLE patients was measured according to the ECLAM score. In the cohort of SLE patients 63% were positive for the IgG class, 40% for the IgA and 57% for the IgM class specific anti-dsDNA ELISA. Sensitivity (79%) and specificity (99%) for the diagnosis of SLE appeared to be highest for the ELISA measuring all isotypes of anti-dsDNA antibodies. The concentrations of anti-dsDNA isotypes showed a strong correlation with disease activity. Analysing the relationship between IgG, IgA and IgM anti-dsDNA antibody isotypes and clinical manifestation, we found a significant association of the IgM isotype with cutaneous involvement and of the IgG isotype with lupus nephritis. The IgG/IgM ratio of anti-dsDNA antibodies represented a significant parameter to distinguish patients with lupus nephritis from those without renal involvement. In the longitudinal study, a continuous ratio under 0.8 was associated with absence of renal involvement throughout the investigated period. In conclusion, the evaluation of anti-dsDNA isotypes provides a diagnostic tool to define subsets within SLE patients with different clinical manifestations. In particular, the IgG/IgM ratio of anti-dsDNA antibodies could be used as a prognostic marker for lupus nephritis during the course of the disease.     

Autoantibody and idiotype profile of lung involvement in autoimmune rheumatic disease.

Several reports have linked the presence of certain serum autoantibodies with particular clinical manifestations of autoimmune disease. For example, the Jo-1 antibody is now established as a marker for fibrosing alveolitis in polymyositis. To investigate the possible association of further autoantibodies or idiotypes with fibrosing alveolitis in autoimmune rheumatic disease a panel of autoantibodies was measured in serum samples from 28 patients with systemic lupus erythematosus (SLE) (10 with and 18 without lung involvement), 21 patients with scleroderma (12 with fibrosing alveolitis and nine without), and 41 patients with 'lone' fibrosing alveolitis. Antibodies measured were IgM and IgG anti-dsDNA and anti-ssDNA antibody; IgG and IgM anticardiolipin antibody; anti-poly (ADP-ribose) antibody; antibodies to two common idiotypes of anti-DNA antibodies, designated 134 and 16/6; and IgM, IgG, and IgA isotypes of rheumatoid factor. None of these antibodies was specifically associated with lung involvement in SLE or scleroderma, but a trend was found towards an increase in all autoantibodies in association with lung disease in SLE, while the reverse trend was seen in scleroderma.     

C3c-binding in inflammatory rheumatic diseases

Sera from 73 patients, 24 with rheumatoid arthritis (RA), 10 with Sj?gren's syndrome (SS, 4 with and six without RA), 17 with Reiter's syndrome (RS), 10 with systemic lupus erythematosus (SLE), 9 with Yersinia arthritis (YA), and 3 with mixed connective tissue disease (MCTD) were examined by enzyme-immunoassay (EIA) for the presence of C3c-binding IgG, IgM, and IgA activity (C3cBIgG, C3cBIgM, C3cBIgA). This activity probably consists of immunoconglutinins and immunoglobulin aggregates. Significantly elevated C3cBIgG was found in the sera of patients with RA (p less than 0.01), SS, and SLE (p less than 0.02). C3cBIgM was elevated in SS and SLE (p less than 0.02). C3cBIgA was increased in RA (p less than 0.005), in SS and YA (p less than 0.02). Correlations of C3c-binding with erythrocyte sedimentation rate, hemoglobin, C-reactive protein, IgG-binding onto platelets, serum IgG, IgM, and IgA levels, and with rheumatoid factors of IgM and IgA classes were computed. C3cBIgG, C3cBIgM, and C3cBIgA correlated significantly with each other, but usually not with other laboratory variables. The exceptions were positive correlations of C3cBIgM with IgM-rheumatoid factors in RA (p less than 0.05), and with serum IgM levels in the whole series of patients (p less than 0.05). The use of C3c represents a new principle to detect abnormalities in the sera of patients with inflammatory rheumatic diseases. However, the pathogenic significance of elevated C3c-binding remains unknown.     

Relationship of renal histopathology in SLE nephritis to immunoglobulin class of anti-DNA

Using a newly-developed solid-phase radioimmunoassay for DNA-binding immunoglobulins, immunoglobulin M (IgM), immunoglobulin G (IgG) and immunoglobulin A (IgA) anti-DNA were measured in serums from 11 patients with active untreated systemic lupus erythematosus (SLE) with nephritis. All patients underwent renal biopsy and were classified according to standard criteria as having diffuse or focal proliferative glomerulonephritis. Although both groups had almost identical total anti-DNA (13.1 versus 13.9 μg/ml, respectively), the IgM to IgG ratio was significantly higher (p < 0.01) in the group with DPGN (7.51) than in the group with FPGN (1.10). We suggest that the switchover mechanism from IgM to IgG antibody production is more profoundly impaired in SLE with severe renal disease than in SLE with mild renal disease.     

Anti-beta2-glycoprotein I: prevalence, clinical correlations, and importance of persistent positivity in patients with antiphospholipid syndrome and systemic lupus erythematosus

OBJECTIVE: Antibodies to beta2-glycoprotein I (anti-beta2-GPI) are found in a large percentage of patients with primary or secondary antiphospholipid syndrome (APS). Our aim was to identify the prevalence and clinical correlation of these antibodies in patients with APS and systemic lupus erythematosus (SLE), in comparison to anticardiolipin (aCL) and the lupus anticoagulant (LAC). We investigated whether serial samples improve clinical utility. METHODS: Serum samples for anti-beta2-GPI (IgG, IgM, IgA), aCL (IgG, IgM, IgA), and LAC (by dilute Russell viper venom time; RVVT) were collected from 418 consecutive patients with SLE or APS between October 2002 and March 2003. Clinical and serologic data of these patients were analyzed. RESULTS: A total of 185 (44.5%) patients were positive for anti-beta2-GPI, 55.3% were positive for aCL, and 31.1% for LAC. Anti-beta2-GPI was more common in Caucasians than in African Americans (p = 0.098). IgM and IgA were the most frequent isotypes of anti-beta2-GPI. aCL and anti-beta2-GPI were highly associated (p < 0.0001 to p = 0.0177, depending on isotype). A positive association was found between the presence of the LAC by dilute RVVT and anti-beta2-GPI IgG (p < 0.0001), IgM (p < 0.0001), and IgA (p = 0.0002) antibodies. Persistent positivity increased the association of venous and arterial thrombosis with anti-beta2-GPI (IgG and IgM isotypes). Pregnancy loss, seizures, and migraines were not associated with anti-beta2-GPI. IgA anti-beta2-GPI was not significantly associated with any manifestation of APS. CONCLUSION: The prevalence of anti-beta2-GPI IgM and IgA was very high in our population. Measurement of anti-beta2-GPI IgG is clinically useful in identifying patients with SLE at higher risk for venous and arterial thrombosis. Persistent positivity increased the association of IgG anti-beta2-GPI with venous thrombosis and anti-beta2-GPI IgM with arterial thrombosis. IgA anti-beta2-GPI was not significantly associated with APS manifestations.     

High prevalence of immunoglobulin A antibody against Epstein-Barr virus capsid antigen in adult patients with lupus with disease flare: case control studies

OBJECTIVE: Systemic lupus erythematosus (SLE) is a severe autoimmune disease with rare remission and recurrent flare. Epstein-Barr virus (EBV) infection has been reported to be strongly associated with SLE in the United States, but with an inconclusive role in Asia. We investigated the role of EBV infection in patients with SLE in Taiwan, with one of the highest population densities in Asia. METHODS: We conducted case-control studies to test whether EBV infection was associated with adult SLE in Taiwan. In the first study, 36 adults with SLE and 36 sex and age matched controls were enrolled for examination of serum IgG, IgM, and IgA antibody against EBV-virus capsid antigen (EBV-VCA). In the second study, another 36 adult lupus cases and 36 matched controls were enrolled to confirm the high prevalence of IgA antibody against EBV-VCA found in the first study. Further, both groups of SLE patients were combined to analyze the association between the existence of IgA antibody against EBV-VCA and disease activity (determined by SLEDAI score) and disease flare in patients with SLE. RESULTS: In the first study, IgA antibody against EBV-VCA was the only marker with significantly higher prevalence in adults with SLE compared to healthy adults (36.1% vs 5.6%; p < 0.005). In the second study, we confirmed that the prevalence of IgA antibody against EBV-VCA was indeed higher in adults with SLE (38.9% vs 2.8%; p < 0.001). With further analysis (pooling analysis), adult SLE patients with IgA antibody against EBV-VCA had higher disease activity compared to SLE patients without IgA antibody against EBV-VCA (SLEDAI 7.8 +/- 6.6 vs 3.3 +/- 2.1; p < 0.001). SLE patients with flare showed much higher prevalence of IgA antibody against EBV-VCA compared to those without flare (81.3% vs 25.0%; p < 0.001). CONCLUSION: This is the first evidence that IgA antibody against EBV-VCA is strongly associated with disease flare in SLE patients. It suggests that EBV reactivation may contribute toward the disease flare of SLE.     

Clinical manifestations and antiphosphatidylserine antibodies in patients with systemic lupus erythematosus: is there an association?

Objective: Antiphospholipid antibodies are a group of heterogeneous autoantibodies which have been reported in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) in association with thrombosis, fetal loss, and thrombocytopenia. In this study, we aimed to reveal the prevalence and correlation of IgG, IgA, and IgM isotypes of antibodies to cardiolipin (aCL) and antiphosphatidylserine (aPS) with clinical and laboratory manifestations of SLE patients. Methods: Fifty-nine SLE patients and 41 healthy controls were included. Fifteen of patients (25.4%) had secondary APS. aCL and aPS antibody assays were performed by enzyme-linked immunosorbent assay. Results: All isotypes of aCL and aPS antibodies except IgG were higher in patients with or without APS than those in the healthy controls (p<0.001). The most significant associations were found among migraine and IgA aCL (p<0.001), livedo reticularis and both IgM aCL and IgM aPS (p<0.001), migraine and IgM aCL (p<0.01), pulmonary involvement and IgM aCL (p<0.01), migraine and IgA aPS (p<0.01), and both thrombosis and migraine with IgM aPS (p<0.01). Conclusion: A relatively high prevalence of aCL and aPS antibodies was found in our SLE patients. It seems that isotypes of IgM aCL, IgM aPS, IgA aCL, and IgA aPS antibodies are correlated well with migraine and IgM aPS with thrombosis in SLE patients with secondary APS. The assessment of both IgM and IgA isotypes of aPS and aCL antibodies may be helpful in predicting these manifestations.     

Anti-dsDNA antibodies in Brazilian patients of mainly African descent with systemic lupus erythematosus: lack of association with lupus nephritis

Renal disease is associated with morbidity and mortality in systemic lupus erythematosus (SLE) and anti-dsDNA antibodies with SLE immunopathogenesis. We investigated the dsDNA antibody profile of 84 Brazilian SLE patients, 27 with lupus nephritis. Thirty-six (39.1%) patients had dsDNA IgG antibodies shown in enzyme-linked immunosorbent assay (454.7 ± 281.1 WHO units/mL), nine presenting renal disease. The following profile of dsDNA antibodies was demonstrated in Crithidia luciliae test: IgA (seven out of 36; 19.4%), IgG (22 out of 36, 66.1%); IgM (nine out of 36, 25.0%), and IgE (four out of 36, 11.1%). Two or three isotypes of dsDNA antibodies were observed in nine (25.0%) patients, while 11 (30.5%) were seronegative in the C. luciliae test. Patients with dsDNA antibodies had lower serum C3 and C4 when compared with SLE individuals without these immunoglobulins (P < 0.01 and P < 0.001, respectively). There was no association between any dsDNA antibody isotype and lupus kidney disease nor was anti-dsDNA IgM antibody associated with absence of nephritis.     

IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF detected by ELISA in rheumatoid arthritis.

One hundred patients with rheumatoid arthritis (RA), of whom 73 were seropositive by latex or Waaler-Rose (WR) assays, or both, 100 healthy subjects, and 102 diseased controls (22 patients with systemic lupus erythematosus (SLE) and 80 with bronchial asthma) were evaluated for the presence of IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF by an enzyme linked immunosorbent assay (ELISA). Ninety two per cent, 65%, 68%, and 66% of the patients with RA were found to be positive for IgM, IgA, IgE, and IgG respectively. A positive correlation existed between the levels of IgM RF and IgA RF on the one hand and disease activity on the other, and the levels of IgM RF and IgA RF correlated with the levels of circulating immune complexes as measured by a C1q binding assay. The presence of extra-articular features also correlated positively with the levels of IgA RF and IgE RF. Five out of six patients with Sjögren''s syndrome had very high levels of IgA RF. Of 47 patients typed for HLA-DR, DR1 and DR2 were significantly more frequent in those with the highest levels of IgM RF. Conversely, DR3 was associated with low levels or absence of IgA RF and IgE RF. These results suggest that immune response genes may regulate the level of different RF isotypes. The frequencies of IgM, IgA, IgE, and IgG RF were 59%, 36%, 9%, and 27% respectively in SLE and 25%, 2.5%, 70%, and 59% in bronchial asthma.