Is the target of anti-cardiolipin antibodies the same in Gougerot-Sj?gren syndrome and lupus erythematosus disseminatus?

Forty-seven patients were diagnosed as having systemic lupus erythematosus (SLE) and 34 patients primary Sj?gren's syndrome (SS); 30 controls were also studied. Anti cardiolipin (CL), anti double-stranded DNA (ds DNA) and anti single-stranded DNA (ss DNA) antibodies were determined by the enzyme-linked immunosorbent assay. Elevated anti-CL antibody levels were detected in 47.8 p. 100 (n = 46) of patients with SLE and in 85.3 p. 100 (n = 34) of patients with SS, but only once in controls. Elevated ss DNA were detected in 91.5 p. 100 (n = 47) of patients with SLE and in 18.3 p. 100 of patients with SS but never in controls. Elevated anti-ss DNA were detected in 93.3 p. 100 and 97.1 p. 100 respectively of patients with SLE and SS and in 3.3 p. 100 of controls. There was no correlation between anti-CL and thrombosis, circulating lupus anti coagulant or VDRL. The most striking association, however, was between anti-CL and anti ss-DNA antibodies in SLE. There was no correlation between anti-CL and anti ds-DNA antibodies in SLE patients. Anti CL antibodies were correlated both to ss-DNA and anti ds-DNA in SS patients. Absorption of positive anti-CL antibodies sera were done on DNA (ss-DNA and ds-DNA) affinity column chromatography: anti-CL antibodies were absorbed only by ss DNA in SLE and by both ss DNA and ds DNA in SS.     

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.     

Measurement of anticardiolipin antibodies and its significance in systemic lupus erythematosus

A method for detection of anticardiolipin (ACL) antibodies with enzyme-linked immunosorbent assay was developed. Microtitre plates were coated with cardiolipin at a concentration of 20 micrograms/ml by evaporation under 4 degree centigrade overnight. Non-specific binding of diluted sera was eliminated by blocking of plates with 10% fetal calf serum in phosphate buffered saline (FCS/PBS) for 2 hours at room temperature. Sera (50 microliters/well) at a dilution of 1:100 were incubated for 2 hours at room temperature. Horseradish peroxidase conjugated rabbit anti-human IgG, IgM, IgA at a dilution of 1:2000, 1:1000, 1:500 respectively was added to the wells, and incubated for one and half hours at room temperature. The results were read at 490nm after incubation with substrates at 37 degree centigrade. 85 patients with systemic lupus erythematosus (SLE), 45 with rheumatoid arthritis (RA), 25 with progressive systemic scleroderma (PSS), and 18 primary Sjogren's syndrome were tested. The frequency of ACL antibody in SLE (48%) was much higher than that in RA (11%), PSS (12), SS (5.5). Three isotypes of ACL (IgG, IgM, IgA) were detected in the study with predominance of IgG isotype. ACL antibody was significantly associated with thrombosis, cutaneous vasculopathy, thrombocytopenia, and spontaneous abortion in patients with SLE. Strong relationship between ACL antibody and lupus anticoagulant was found. There was no correlation between ACL and anti-DNA antibodies, nor was ACL and VDRL test. The level of ACL antibody could be reduced by use of corticosteroids.     

Heterogeneity of antibodies to beta2-glycoprotein 1 from patients with systemic lupus erythematosus

We studied antibodies to beta2-glycoprotein 1 (anti-beta2GP1) from 72 patients with systemic lupus erythematosus (SLE) with or without antiphospholipid syndrome (APS) or with or without anticardiolipin antibodies (aCL). Fifteen patients had APS and positive antiphospholipid antibodies [clinical APS(+)/aPL(+)], 12 patients had APS, negative serum IgG and IgM aCL, antiphosphatidylethanolamine, anti-phosphatidylserine and no lupus anticoagulant [clinical APS(+)/ aPL(-)]. A third group included 16 patients without APS but high aCL levels [clinical APS(-)/ aPL(+)]. In a fourth group we studied 29 patients without clinical manifestations of APS or aCL [clinical APS(-)/aPL(-)]. One hundred anticardiolipin and VDRL-negative normal sera were studied as controls. IgG antibodies to cardiolipin proper in a bovine beta2GP-free system, to human beta2GP1 immobilized on cardiolipin or to human beta2GP1 alone were detected in all sera by ELISA using irradiated and nonirradiated plates from two manufacturers. Sera from APS(+)/aPL(+) patients showed IgG binding to CL, CL + beta2GP1 and beta2GP1 in irradiated and nonirradiated plates. APS(+)/ aPL(-) sera had more significant IgG binding to beta2GP1 than normal controls when studied in both irradiated or nonirradiated plates (P = 0.001). This binding was inhibited by solid-phase cardiolipin in a dose-dependent manner. Sera from the APS(-)/aPL(+) subgroup had comparable IgG activity in both the CL and CL + beta2GP1 assays, while no anti-beta2GP1 activity was detected in these sera. Sera from the clinical APS(-)/aPL(-) patients were negative in the three ELISA systems. Antibodies to human beta2GP1 from SLE patients recognize various epitopes. Those from APS(+)/ aPL(+) patients appear to react with an epitope boosted by cardiolipin in addition to another one present in the native protein. In contrast, anti-beta2GP1 from patients with APS(+)/aPL(-) are blocked by cardiolipin, suggesting that their epitope is the phospholipid-binding site.     

Anticardiolipin Antibodies in Juvenile Rheumatoid Arthritis and Systemic Lupus Erythematosus

Background: Antiphospholipid antibody syndrome (APS) can either occur as a primary syndrome or associated with other autoimmune diseases such as systemic lupus erythematosus (SLE). Anticardiolipin antibody (aCL) of IgG and/or IgM isotype in blood, measured by a standardized ELISA is the most acceptable laboratory criteria. APS IgG isotype, particularly IgG2 subclass is more strongly associated with thrombosis. Objectives: This study was done to determine the prevalence of IgG aCL and its subclasses in relation to APS symptoms, in a group of juvenile rheumatoid arthritis (JRA) and juvenile systemic lupus erythematosus (SLE) patients.   Methods: In this prospective study, 28 JRA and 16 SLE patients, aged 3-18 years, were enrolled. IgG aCL was assayed by standard aCL ELISA. IgG subclasses were also assayed by ELISA on sera with medium to high titers of aCL. ACL assay was performed on at least two occasions for each patient, over 3-6 months period of follow up.   Results: 29% (8/28) of JRA patients and 44% (7/16) of SLE patients had aCL. Six of SLE patients displayed APS related manifestations: hemolytic anemia, thrombocytopenia, arterial occlusion, valvular heart disease, livedo reticularis and pulmonary hypertension, but none of them had persistant medium or high titer of aCL. The lack of association of high titer of aCL with APS related symptoms was observed in two patients. The IgG subclasses were primarily IgG1 and IgG3.   Conclusion: The prevalence of IgG aCL in this group of pediatric SLE and JRA is not uncommon but it’s relation to clinical manifestations is not clear. IgG1 and IgG3 subclasses were not associated with thrombosis, which is in agreement with previous studies.     

Anti-phospholipid antibodies and thrombotic thrombocytopenic purpura

Anti-phospholipid antibodies were measured in 9 patients with active thrombotic thrombocytopenic purpura (TTP). 8 patients had primary TTP and one had TTP secondary to systemic lupus erythematosus (SLE). No patient showed circulating 'lupus' anticoagulants or false positive tests for syphilis. A solid phase immuno-assay for anti-cardiolipin antibodies (ACA) gave negative results in the patient with secondary TTP as well as in all but one case with primary TTP. ACA of IgG class were not found in any TTP patient while they were present in 10 out of 18 patients suffering from thrombocytopenia with active SLE. These data indicate that anti-phospholipid antibodies do not have a role in the development of thrombosis and thrombocytopenia with TTP.     

系统性红斑狼疮患者抗心磷脂抗体滴度变化与临床特点的分析

目的 探讨血清抗心磷脂抗体(ACA)滴度的变化对系统性红斑狼疮(SLE)患者临床特征的影响.方法 采用酶联免疫吸附试验(ELISA)对85例SLE患者重复检测ACA.根据其ACA滴度变化分为A、B 2组,A组患者ACA持续阳性.B组患者ACA转阴,分析ACA滴度变化与临床特点的相关性.结果 A组37例,B组48例.血小板减少的发生率A组为41%,B组为19%,差异有统计学意义(P<0.05);A组血小板计数为(24±6)×109/L,B组血小板计数为(46±10)×109/L,差异有统计学意义(P<0.05).A组11%患者出现血栓,B组患者无血栓发生,A组患者血栓发生率高于B组,差异有统计学意义(P<0.05).心脏瓣膜病变A组19%,B组为4%,差异有统计学意义(P<0.05). A组狼疮抗凝物(LA)阳性率32%,B组13%.差异有统计学意义(P<0.05).2组患者雷诺现象、肺动脉高压、狼疮肾炎等临床表现发生率的差异无统计学意义(P0.05).结论 部分ACA阳性患者随着SLE病情的改善其ACA转阴,ACA持续阳性患者血栓形成、血小板减少、心脏瓣膜病的发生率和LA阳性率高于ACA转阴的SLE患者,ACA持续阳性或ACA转阴的变化与SLE患者的其他临床特征无显著相关性.     

Profile and cross-reactivities of antiphospholipid antibodies in systemic lupus erythematosus and syphilis

Summary Antiphospholipid antibodies have been determined in two groups of 48 sera from patients with systemic lupus erythematosus (SLE) and syphilis. Using an ELISA, IgG anticardiolipin (CL), antiphosphatidyl serine (PS) and antiphosphatidyl ethanolamine (PEA), antibodies have been detected with the same frequency in both groups of patients. Titres of antiphosphatidyl serine (PS) (p<0.005) and PEA antibodies (p<0.05) were significantly higher in the syphilitic sera compared to the SLE sera. Anticardiolipin binding activity of both groups of sera could be inhibited by preincubation with phosphatidic acid, phosphatidyl serine, phosphatidyl glycerol and cardiolipin antigens, but the inhibiting ratio of phosphatidyl antigen was significantly higher (p<0.01) in the SLE group. These data suggest that anticardiolipin auto-antibodies present in SLE sera are very similar to the reagins or antibodies to cardiolipin seen in syphilitic sera. IgG anticardiolipin antibodies may be an epiphenomenon and are probably not implicated in the pathogenesis of the thrombotic diathesis seen preferentially in some patients with SLE.     

Studies of IgG, IgM and IgA antiphospholipid antibody isotypes in systemic lupus erythematosus

We evaluated the clinical relevance of 6 antiphospholipid antibodies including cardiolipin and their IgG, IgM and IgA isotypes in 92 patients with systemic lupus erythematosus (SLE). Antiphospholipid antibodies generally had significant associations with thrombocytopenia and a history of false-positive syphilis serologies. In 4 of 6 antiphospholipid antibodies, an inverse association with renal disease was observed. Antiphospholipid antibodies may moderate or protect against renal disease, or this may reflect the high doses of corticosteroids and cytotoxic drugs received by this group. Further studies are needed to determine how many antibody families cause these activities and to elucidate whether certain SLE subgroups possess differing specificities for each of the phospholipids.     

Identification and characterization of a peptide mimetic that may detect a species of disease-associated anticardiolipin antibodies in patients with the antiphospholipid syndrome

OBJECTIVE: To test the feasibility of applying a mimetic (specific for a patient-derived prothrombotic anticardiolipin antibody [aCL]) to study the homologous, disease-associated aCL in patients with antiphospholipid syndrome (APS). METHODS: We used the CL15 monoclonal aCL to screen 17 phage-display peptide libraries. Peptides (corresponding to recurrent peptide sequences) and their derivatives were synthesized and analyzed for binding to CL15 and for their abilities to inhibit CL15 from binding to cardiolipin. A peptide was chosen and used to study CL15-like IgG aCL in plasma samples from patients with APS, patients with systemic lupus erythematosus (SLE) but without APS, and normal healthy donors. RESULTS: Library screening with CL15 yielded 4 recurrent peptide sequences. Analyses of peptides showed that peptide CL154C reacted with antibody CL15 and inhibited binding of CL15 to cardiolipin, indicating that peptide CL154C may be a peptide mimetic for the CL15 aCL. Initial studies with plasma samples revealed that CL154C-reactive IgG was present (positivity defined as the mean + 3 SD optical density of the 25 normal controls) in 15 of 21 APS patients and 1 of 12 SLE patients. CONCLUSION: These findings suggest that it is feasible to develop a specific enzyme-linked immunosorbent assay for each immunologically and functionally distinct disease-associated aCL. Additional testing of CL154C with a larger number of APS patients and SLE patients, as well as identification of peptide mimetics for each distinct aCL, will reveal the diagnostic potential of CL154C and other mimetics in identifying patients with aCL who are at risk of developing life-threatening thrombosis.     

Autoantibodies in systemic lupus erythematosus and normal subjects

Summary The presence of various antibodies in serum samples from patients with systemic lupus erythematosus (SLE) and from healthy subjects was investigated by ELISA, using a panel of natural antigens. Fifty-eight serum samples from 58 healthy women and 50 serum samples from 30 patients with active SLE were tested with 9 natural antigens (ds-DNA, actin, tubulin, thyroglobulin, myosin, myoglobin, human transferrin, human interferon a and BSA FV). It was found that the proportion of positive sera from healthy women at a dilution of 1/20 was almost the same as that of lupus sera at a dilution of 1/150 for nearly all antigens, while at a dilution of 1/150 the proportion of positive sera from patients with SLE was significantly higher for nearly all antigens. In lupus sera a high degree of correlation was observed between titers of anti-DNA and titers of the other antibodies. One hundred eighty-eight serum samples from 53 SLE patients, taken during exacerbation and remission of the disease were tested with ds-DNA, actin and tubulin. Antibodies (IgG) to ds-DNA actin and tubulin were found in the majority of serum samples taken during the active phase of the disease. On the other hand, very few serum samples taken during remission were found to be positive. A high degree of correlation was found between the OD of anti-actin/anti-ds-DNA (r=0.769) and anti-tubulin/anti-ds-DNA (r=0.829). In a competitive enzyme immunoassay for DNA, actin, tubulin, myosin and thyroglobulin, a high degree of inhibition was observed with the homologous antigens. Cross inhibition was observed between actin, tubulin and myosin, and to a lesser degree with DNA. These results indicate that normal sera contain low titers of auto and foreign antibodies while active SLE sera react strongly with the same antigens.     

Clinical features associated with a positive anticardiolipin antibody in Irish patients with systemic lupus lrythematosus

Summary Anticardiolipin antibodies (ACA) are one of a number of autoantibodies found in patients with systemic lupus erythematosus (SLE) and their presence has been associated with clinical features of the antiphospholipid syndrome (APS). The aim of this study was to determine which clinical features are associated with a positive anticardiolipin antibody in Irish patients with SLE. Ninety-five Irish patients with SLE were studied. All were examined thoroughly, had their full history taken, and had case records reviewed. The presence of any clinical feature associated with the APS was noted. Sera from these patients were tested for IgG and IgM ACA. The only significant association found was between a history of venous thrombosis and the presence of ACA, although several other features were more common in ACA positive patients. There were no significant associations with one or other isotype. This study serves as a reminder to consider the possibility of venous thrombosis, and other clinical features, if an SLE patient is positive for ACA.     

ANTICARDIOLIPIN ANTIBODIES, HAEMOLYTIC ANAEMIA AND THROMBOCYTOPENIA IN SYSTEMIC LUPUS ERYTHEMATOSUS

Anticardiolipin antibody (ACA) levels were determined in 17Asian female SLE patients with autoimmune haemolytic anaemia(AIHA) and 29 Asian female SLE inpatients without AIHA (controlpatients). Both IgG and IgM isotypes were measured by ELISA.Elevated IgM APA titres (>5 SD of normal health controls)were seen in 11 (64.7%) of 17 AIHA patients and six (20.7%)of 29 control patients(P<0.01). There was no significantdifference in IgG ACA titres between the two groups. Thrombocytopeniawas present in 11 (64.7%) of the AIHA patients and nine (31%)of the control patients (P<0.05). None of the control SLEpatients with thrombocytopenia had raised IgM ACA levels andonly one had an elevated IgG ACA titre. Autoimmune haemolyticanaemia occurring in the context of SLE frequently associatedwith the concomitant presence of thrombocytopenia (Evan's syndrome)and with the presence of ACA. KEY WORDS: Cardiolipin, Anticardiolipin antibody, ELISA, Evans' syndrome, Direct antiglobulin test, Thrombocytopenia, Systemic lupus erythematosus     

系统性红斑狼疮抗活化的蛋白C研究

目的　了解抗活化的蛋白C(APCR)在系统性红斑狼疮 (SLE)患者中的发生情况 ,并进一步探讨SLE患者发生血栓的机制。方法　采用APC KPTT法 ,ELISA法和PTT LA法分别对5 0例SLE患者及 2 0例正常对照 (NC)进行APCR、抗心磷脂抗体 (ACA)和狼疮抗凝物 (LA)检测。结果　SLE患者APCR阳性率 ( 5 8% )明显高于NC组 ( 5 % ) (P <0 0 0 5 ) ,APCR阳性患者中血栓发生率( 2 7 6% )明显高于APCR阴性患者 ( 4 8% ) (P <0 0 1) ,患者LA阳性率 ( 2 2 % )明显高于对照组 ( 0 /10 ) (P <0 0 5 ) ,患者ACA IgG及IgM明显高于对照组 (P <0 0 5 ) ,而IgA与对照组差异不显著 (P >0 0 5 ) ,LA阳性组中的APCR阳性率 ( 90 9% )明显高于LA阴性组 ( 5 3 8% ) (P <0 0 5 ) ,ACA阳性组中的APCR阳性率 ( 64 7% )与ACA阴性组 ( 60 6% )未发现明显相关性 (P >0 0 5 )。结论　APCR在国人SLE患者中有较高的发生率且与LA有明显相关性 ,APCR可能是SLE患者诱发血栓的主要原因之一。     

Anti-ribosomal P protein antibodies detected by immunoblotting in patients with connective tissue diseases: their specificity for SLE and association with IgG anticardiolipin antibodies

OBJECTIVE: To assess the prevalence and clinical and serological associations of anti-ribosomal P protein antibodies (anti-P antibodies) in patients with connective tissue diseases (CTDs) and investigate the immunobiological nature of autoantibody clustering in which anti-P antibodies play a part. METHODS: IgG anti-P antibodies in the sera of 267 patients with CTDs and 31 healthy subjects were analysed by immunoblotting performed on cytoplasmic extract of Raji cells. 60 patients with systemic lupus erythematosus (SLE), 32 systemic sclerosis, 46 primary Sj?gren's syndrome, 16 poly/dermatomyositis, 11 rheumatoid arthritis, 8 undifferentiated CTD, 72 overlap CTD, and 22 primary antiphospholipid syndrome were studied. Anti-P antibodies were affinity purified by elution from nitrocellulose bound antigen and tested by ELISA for their binding activity to cardiolipin. RESULTS: Anti-P antibodies were detected in 16 (6%) patients and in none of the controls: 12/60 SLE (20%) and 4/80 undifferentiated/overlap patients with CTD (5%). A close association of IgG antibodies with P proteins and with cardiolipin was seen in lupus sera (p=0.0009, odds ratio 18.33). Anti-P antibodies from 9 of 12 anti-P lupus serum samples could be affinity purified and none of the affinity purified fractions cross reacted with ELISA plate coated cardiolipin. CONCLUSIONS: Anti-P immunoreactivity is a specific marker of SLE and lupus-like disease and its detection is recommended as a powerful diagnostic tool. Anti-P antibodies are strongly clustered with IgG anticardiolipin antibodies in lupus sera, even if they are independently elicited. This suggests that their cognate autoantigens play a part in a common pathogenetic pathway in SLE.     

Significance of antibodies to cardiolipin in unselected patients with systemic lupus erythematosus: clinical and laboratory associations

In a multicentre study anticardiolipin antibodies of the IgG and IgM isotypes were measured by a solid phase enzyme immunoassay in 368 patients with systemic lupus erythematosus (SLE) who were not selected on the basis of features of antiphospholipid syndrome. Clinical and laboratory associations of increased levels of anticardiolipin antibodies were evaluated. IgG and IgM antibodies to cardiolipin were documented in 224 (60.9%) and 128 (34.8%) patients, respectively. Regarding the symptoms of antiphospholipid syndrome, elevated amounts of anticardiolipin IgG were significantly associated with spontaneous abortion (P<0.001), thrombocytopenia (P<0.01), livedo reticularis (P<0.01) and a positive direct Coombs test (P<0.05), but not with thrombosis or central nervous system diseases such as epilepsy and psychosis. IgM antibodies to cardiolipin were associated with a positive direct Coombs test (P<0.01), but with no other symptom of antiphospholipid syndrome. The predictive values of anticardiolipin antibody determinations in unselected SLE patients were poor for all features of antiphospholipid syndrome because of high proportions of false-positive and false-negative results. As for other manifestations of SLE, positive correlations between raised antibodies to double-stranded DNA and the occurrence of anticardiolipin antibodies of the IgG isotype were observed, and anticardiolipin IgM was negatively associated with nephritis.     

Relation of antivimentin antibodies to anticardiolipin antibodies in systemic lupus erythematosus.

Tests for antivimentin antibodies (AVA) were performed on 50 systemic lupus erythematosus (SLE) and 63 control sera by indirect immunofluorescence and enzyme linked immunosorbent assay (ELISA). The prevalence was significantly raised in SLE (38% and 50% of sera positive for IgM-AVA and IgG-AVA, respectively, by immunofluorescence; 36% and 64% of sera positive for IgM-AVA and IgG-AVA, respectively, by ELISA) in comparison with the control sera. A significant correlation existed between IgM-AVA, on the one hand, and anticardiolipin antibodies (ACA) and anti-single-stranded DNA (ssDNA), on the other. A stepwise principal component analysis demonstrated that IgM-AVA and IgG-AVA accounted for 71% of the total variance in SLE (50 patients x 5 parameters = total variance). Twenty ACA positive serum samples from patients with syphilis were therefore tested for the presence of AVA, but hardly any were found to be positive. IgM-AVA from patients with SLE were inhibited by cardiolipin and absorbed with ssDNA. An association between AVA positivity and arthralgia was also shown in SLE.     

Lupus anticoagulant: clinical significance in anticardiolipin positive patients with systemic lupus erythematosus.

The significance of anticardiolipin antibodies and the lupus anticoagulant was studied in 58 consecutive patients with systemic lupus erythematosus. On 85 occasions serum IgG and IgM anticardiolipin antibodies were measured by an enzyme linked immunosorbent assay (ELISA), and simultaneous plasma samples tested for lupus anticoagulant activity. The most significant association with clinical events (previous thrombosis or thrombocytopenia occurring in 11/58 patients) was with prolonged tissue thromboplastin inhibition time (TTIT) followed by prolonged kaolin cephalin clotting time (KCCT) then raised IgG anticardiolipin antibody concentrations and dilute Russell's viper venom time. Although IgG anticardiolipin antibodies or KCCT were the most sensitive tests in identifying this group, the TTIT was the most specific (98%). Nine patients were IgG anticardiolipin antibody positive and lupus anticoagulant negative, of whom one had thrombocytopenia but none had thrombosis. The presence of a lupus anticoagulant in anticardiolipin antibody positive patients increases specificity for certain adverse clinical events.     

DNA antibodies and complement in SLE patients

Sixty-seven patients with systemic lupus erythematosus (SLE) were followed up for 3-19 months (mean 12) in a prospective study. The activity of SLE was estimated on clinical grounds and correlated with DNA antibody and complement levels. The disease reactivations consisted mostly of articular and cutaneous symptoms. There were 17 relapses and 22 complicating infections during the follow-up period. The levels of antibodies to native, double-stranded (ds) DNA (P less than 0.001) and antibodies to denatured, single-stranded (ss) DNA of IgG class (P less than 0.001) and C3 (P less than 0.001) correlated best with disease activity, which was estimated on the clinical symptoms and signs. These assays were not reliable, however, in predicting minor exacerbations. The levels of IgM class ss-DNA antibodies were significantly higher in SLE patients without nephritis than in SLE nephritis patients. In most cases, the combination of IgG class ss-DNA antibody and complement (C3 and CH50) determinations differentiated SLE relapse from infection.