Low avidity antibodies to double stranded DNA in systemic lupus erythematosus: a longitudinal study of their clinical significance.

In a longitudinal study the relevance of the detection of low avidity antibodies to double stranded DNA (dsDNA) as measured by the polyethylene glycol (PEG) assay in patients with systemic lupus erythematosus (SLE) was evaluated. It was found that 35 patients positive in the PEG assay only--that is, having only low avidity anti-dsDNA in their circulation, had a mild course of their SLE with absence of renal involvement. The PEG assay had little predictive value but a high specificity (90.2%) for clinical exacerbations; furthermore, a change in avidity of anti-dsDNA in such patients was seldom observed. In 14 patients positive in both Farr and PEG assays--that is, with a relative preponderance of high avidity anti-dsDNA, there was a clear correlation between rises in Farr assay and major exacerbations, while the PEG assay on its own was not helpful in predicting disease manifestations; disease manifestations were often heralded by a change in the Farr/PEG ratio, with renal and cerebral exacerbations associated with the greatest increase in the Farr/PEG ratio (more than 10 times the previous value).     

Anti-dsDNA antibody avidity determination by a simple reliable ELISA method for SLE diagnosis and monitoring

High avidity anti-dsDNA antibodies are more specific for SLE diagnosis, and more closely associated with renal involvement than intermediate or low-affinity anti-dsDNA antibodies. ELISA methods are largely used to detect anti-dsDNA, but their high sensitivity is inversely related to specificity because they also detect low avidity antibodies. We developed an ELISA assay based on the law of mass action and the competitive binding of dsDNA in solution and coated to microwells with anti-dsDNA antibodies. A simplified Scatchard plot analysis system was used to measure anti-dsDNA antibody avidity which was expressed as apparent affinity constant (Kaa), and quantified in liters per unit (I/U). We prospectively studied 101 consecutive SLE patients, who were followed for 3 years; three serum samples were sequentially collected from each patient during follow-up for determination of IgG anti-dsDNA antibody concentration, and anti-dsDNA avidity. SLE disease activity was estimated using the European Consensus Lupus Activity Measure (ECLAM) index. Sera from 100 healthy subjects and 133 patients with other connective tissue diseases or infectious diseases were also assayed as controls. The mean Kaa in SLE patients was 65.2 +/- 47.3 l/U, with no variations over time. Anti-dsDNA-positive SLE patients had higher Kaa values (79.1 +/- 46.8) than anti-dsDNA negative patients (27.2 +/- 20.1; P < 0.001). No correlation emerged between anti-dsDNA avidity and the ECLAM activity index score. Avidity was significantly higher in patients with renal involvement vs patients without this complication (78.2 +/- 50 vs 59.9 +/- 45.6 l/U; P = 0.0013). This simple ELISA method could be very useful in the diagnostic phase to differentiate high avidity anti-dsDNA autoantibodies that are characteristically found in SLE patients from low avidity antibodies that can also be found in other inflammatory diseases. Moreover, our data confirm the predictive value of high avidity anti-dsDNA antibodies for the development of lupus nephritis.     

The clinical significance of measuring different anti-dsDNA antibodies by using the Farr assay, an enzyme immunoassay and a Crithidia luciliae immunofluorescence test.

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.     

Detection of anti-dsDNA as a diagnostic tool: a prospective study in 441 non-systemic lupus erythematosus patients with anti-dsDNA antibody (anti-dsDNA).

The diagnostic significance of anti-double-stranded deoxyribonucleic acid (anti-dsDNA) determination was evaluated in a prospective manner from 1974 to 1982 in a group of 441 patients without systemic lupus erythematosus whose sera were found to contain antibodies to dsDNA on routine screening (Farr assay). Within one year 69% (304) of these patients fulfilled the preliminary American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). Eighty-two of the remaining 137 patients were followed up for several years. At the end of the study 52% of these patients had also developed systemic lupus erythematosus. Patients who developed systemic lupus erythematosus were characterised by the occurrence of relatively high avidity anti-dsDNA in the circulation compared with patients who did not develop systemic lupus erythematosus. It can be concluded that about 85% of patients without systemic lupus erythematosus with anti-dsDNA in the circulation will develop SLE within a few years. Taking into account the relative avidity of anti-dsDNA, as determined by calculation of Farr/polyethylene glycol (PEG) ratios, we conclude that patients with relatively high avidity anti-dsDNA are more prone to develop systemic lupus erythematosus than patients with relatively low avidity anti-dsDNA.     

Circulating anti-double-stranded DNA antibody-secreting cells in patients with systemic lupus erythematosus: a novel biomarker for disease activity

Antibodies against double-stranded DNA (dsDNA) are widely used to diagnose systemic lupus erythematosus (SLE) and evaluate its activity in patients. This study was undertaken to examine the clinical utility of circulating anti-dsDNA antibody-secreting cells for evaluating SLE patients. Anti-dsDNA antibody-secreting cells quantified using an enzyme-linked immunospot assay were detected in the spleen, bone marrow and peripheral blood from MRL/lpr but not in control BALB/c mice. Circulating anti-dsDNA antibody-secreting cells were detected in 29 (22%) of 130 patients with SLE, but in none of 49 with non-SLE connective-tissue disease or 18 healthy controls. The presence of circulating anti-dsDNA antibody-secreting cells was associated with persistent proteinuria, high SLE disease activity index and systemic lupus activity measures, and a high serum anti-dsDNA antibody titre measured with an enzyme-linked immunosorbent assay. The positive predictive value for active disease was 48% for circulating anti-dsDNA antibody-secreting cells versus 17% for serum anti-dsDNA antibodies. A prospective cohort of patients with circulating anti-dsDNA antibodies and inactive SLE showed that the cumulative disease flare-free rate was significantly lower in patients with than without circulating anti-dsDNA antibody-secreting cells (p?相似文献   

Association of alpha-actinin-binding anti-double-stranded DNA antibodies with lupus nephritis

OBJECTIVE: Anti-double-stranded DNA (anti-dsDNA) antibodies may contribute to the pathogenesis of glomerulonephritis (GN) by cross-reacting with alpha-actinin in murine models and in some patients with systemic lupus erythematosus (SLE). We therefore sought to determine possible disease associations with serologic and clinical features and to characterize this new autoantibody specificity. METHODS: One hundred patients with SLE were recruited into this multicenter study, as well as 100 rheumatic disease controls and 2,100 healthy blood donors. Clinical disease was evaluated by the SLE Disease Activity Index (SLEDAI; excluding the anti-DNA component). Anti-dsDNA antibodies were detected by conventional enzyme-linked immunosorbent assay (ELISA) and by a commercial enzyme immunoassay (EIA). Anti-alpha-actinin antibodies were detected by ELISA, and their specificity was confirmed by Western blotting and by indirect immunofluorescence using rat kidney sections and mesangial cells as substrates. Highly positive sera were selected for absorption experiments and were affinity-purified for cross-reactivity studies and measurement of antibody avidity. RESULTS: Sera from 62 of the SLE patients had anti-dsDNA antibodies; 21 of these sera also had anti-alpha-actinin antibodies, as compared with 1 of the 38 sera without anti-dsDNA antibodies. Of the 22 patients with anti-alpha-actinin antibodies, 10 had GN, as compared with 14 of the 78 without anti-alpha-actinin antibodies (P < 0.01). In patients with GN, anti-alpha-actinin, but not anti-dsDNA, antibodies correlated with the SLEDAI score (minus the anti-DNA component) and with treatment. The fraction of serum anti-dsDNA antibodies that cross-reacted with alpha-actinin exhibited high avidity for dsDNA, as determined using a commercial EIA for high-avidity anti-dsDNA antibodies and an in-house conventional ELISA. CONCLUSION: The alpha-actinin-binding antibodies are significantly associated with GN in SLE. Whether such autoantibodies may anticipate the development of this complication of SLE remains to be verified.     

Anti-dsDNA: choice of assay in relation to clinical value

Summary Antibodies to DNA are quite specific for systemic lupus erythematosus (SLE) and occur in the majority of SLE patients. Therefore, their detection is an important diagnostic aid to the clinician. Detection of anti-dsDNA may precede the diagnosis of SLE by more than a year. Fluctuations in the level of anti-dsDNA in an individual patient may give important information on the clinical status of the patient. Four of the most important methods developed for the measurement of anti-dsDNA antibodies will be discussed in this paper: the Farr assay, the PEG assay, the indirect immunofluorescence test on Crithidia luciliae and the ELISA. They will also be compared with one commercially available (Farr) assay, the Amersham anti-dsDNA kit. Each method, detects a part of the spectrum of anti-dsDNA antibodies produced by a patient. The Farr assay is the most specific for SLE; however, milder forms of the disease in which patients have only low avidity anti-dsDNA may easily be missed by this technique. Clinically, high avidity anti-dsDNA is related more frequently to the occurrence of nephritis, whereas low avidity anti-dsDNA antibodies are found more often in patients with central nervous system involvement. Traditionally, SLE is considered an immune-complex disease, in which inflammatory processes are initiated by local deposition of DNA/anti-dsDNA complexes. More recently, a major role was thought to be played by crossreactions of anti-dsDNA with tissue constituents. Our current view, however, is that such a crossreactivity plays only a minor role; we postulate that binding to glomerular constituents is caused by anti-dsDNA antibodies complexed with DNA and histones.     

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.     

Is alpha-actinin a target for pathogenic anti-DNA antibodies in lupus nephritis?

OBJECTIVE: Following recent reports that pathogenic murine anti-DNA antibodies bind to alpha-actinin, it was obviously of interest to assess the ability of human pathogenic anti-double-stranded DNA (anti-dsDNA) antibodies to bind this antigen. Both human monoclonal anti-DNA antibodies and antibodies affinity purified from the sera of patients with systemic lupus erythematosus (SLE) were investigated. METHODS: An enzyme-linked immunosorbent assay was established to measure immunoglobulin binding to alpha-actinin. Antibodies binding dsDNA were purified from the sera of SLE patients who either had active renal disease or had never had renal disease. Serum samples were selected at times when the patients' sera exhibited high IgG binding to dsDNA. The binding of supernatants from 3 high-affinity human anti-dsDNA IgG hybridomas (RH14, B3, and DIL-6) and 7 human IgM anti-DNA hybridomas was also investigated. RESULTS: A greater proportion of anti-dsDNA IgG-binding antibodies purified from patients with renal disease bound to alpha-actinin than did those purified from the sera of patients without renal disease. The specificity of binding to the 100-kd alpha-actinin molecule was confirmed by Western blotting. The pathogenic human antibodies RH14 and B3 bound strongly to alpha-actinin, while nonpathogenic DIL-6 bound very weakly. RT84, the IgM antibody that binds dsDNA with the highest affinity, exhibited the greatest binding to alpha-actinin. CONCLUSION: The results of our study support the findings of previous studies using murine anti-DNA monoclonal antibodies, which suggest that pathogenic anti-dsDNA antibodies cross-react with alpha-actinin.     

Anti-nucleosome antibody: significance in lupus patients lacking anti-double-stranded DNA antibody

OBJECTIVE: To investigate the clinical significance of anti-nucleosome antibodies in SLE patients lacking anti-double stranded DNA (dsDNA) antibodies. METHODS: IgG anti-nucleosome antibodies were detected by enzyme-linked immunosorbent assays (ELISA) in the sera of SLE patients. Anti-dsDNA antibodies were measured by Farr assays and ELISA, not only in the samples taken for anti-nucleosome testing, but also in sera obtained regularly during the follow-up. RESULTS: Ninety-eight (76.0%) out of 129 patients with SLE had anti-nucleosome antibodies. Twenty-five patients (19.4%) consistently showed little or no anti-dsDNA reactivity during the course of their disease, and among these anti-nucleosome antibodies were present in the sera of 15 (60.0%). Of the patients with anti-dsDNA-negative SLE, renal disorders were present in 8 patients (32.0%), all of whom had anti-nucleosome antibodies. Renal disorders were not found in patients (n = 10) who had neither anti-dsDNA nor anti-nucleosome antibodies. Other autoantibodies such as anti-Ro, anti-Sm and anti-cardiolipin were not associated with renal disorders in this group. The levels of anti-nucleosome antibody strongly correlated with the SLEDAI scores, but inversely correlated with serum complement levels in anti-dsDNA negative SLE patients. CONCLUSION: Our data suggest that the anti-nucleosome antibody may be a useful marker for diagnosis and activity assessment of anti-dsDNA negative SLE. Anti-nucleosome antibody may be an important factor for renal involvement in this subgroup of patients.     

Cellular control of antinuclear antibody production. Anti-dsDNA and anti-Sm plaque forming cells in SLE patients and normal individuals

The in vitro response of lymphocytes to dsDNA, Sm, and Pokeweed Mitogen (PWM) and the role of monocytes in the control of this response were studied in 21 SLE and 14 healthy individuals. Specific hemolytic plaque assays were used to enumerate peripheral blood B lymphocytes secreting anti-dsDNA and anti-Sm antibodies. After 7 days in tissue culture without stimulation, anti-dsDNA or anti-Sm Plaque Forming Cells (PFC) were observed in 75% of SLE patients and 45% of normals. PWM, dsDNA, and Sm stimulation raised the levels of anti-dsDNA PFC in 25%, 37%, and 83% of SLE cultures respectively, and in all but one normal culture. PWM and dsDNA induced a decrease in anti-dsDNA PFC in 50% and 62% of SLE cultures. This suppressive effect was mainly exerted on spontaneous high producers of anti-dsDNA PFC. Monocyte depletion from cultures resulted in a decrease in PFC formation in all normals studied and in 7 SLE cultures. In 2 SLE cultures with no stimulation and one dsDNA stimulated culture, the number of anti-nuclear PFC increased after monocyte depletion. In cocultures of allogeneic, HLA-DR identical mononuclear cells, dsDNA pulsed SLE monocytes appeared more efficient than pulsed normal monocytes in helping to generate anti-dsDNA PFC. SLE lymphocytes responded less well than normals to dsDNA. These results suggest that: nuclear antigens may act as stimulators or suppressor of the specific autoimmune response, depending on the immune status of the SLE patient; and that abnormalities in both monocyte and lymphocyte responses lead to the excessive secretion of anti-dsDNA and anti-Sm antibodies by SLE B lymphocytes.     

Evidence for direct anti-heparin-sulphate reactivity in sera of SLE patients

Recently it has been suggested that anti-dsDNA antibodies (Abs) promote tissue damage in systemic lupus erythematosus (SLE) by cross-reactivity with highly negatively charged tissue components such as heparan sulphate (HS), the major glycosaminoglycan of the glomerular basement membrane (GBM). Other authors, however, support the theory of DNA-anti-dsDNA immune complex deposition in situ. To further elucidate the possible role of HS antibodies, we developed a new ELISA system with heparan sulphate bound to solid phase. SLE patients (n=40) showed a higher reactivity against HS (mean=28.4, SD=34.3) as compared to normal donors (n=28, mean=15.2, SD=6.3) and patients with rheumatoid arthritis (n=35, mean=14.3, SD=6.4). The addition of native dsDNA or HS to SLE sera was followed by a dose-dependent reduction in anti-HS reactivity. In contrast, in an anti-dsDNA ELISA, no reduction was observed when HS was added to SLE sera. An increase in reactivity was observed when SLE sera with and without a prior incubation with dsDNA were digested with DNAse I or II. After the purification of serum samples by protein A sepharose under dissociative conditions, seven out of eight SLE patients showed an increase in anti-HS reactivity. No correlation of the anti-HS Abs was found with organ involvement or other serological parameters. We concluded, that there is evidence for a direct anti-HS Ab reactivity in SLE sera. A part of these antibodies seems to show low avidity anti-dsDNA cross-reactivity.     

Anti-nucleosome antibodies in patients with systemic lupus erythematosus of recent onset. Potential utility as a diagnostic tool and disease activity marker

OBJECTIVE: To compare the utility of anti-chromatin antibodies for the diagnosis of systemic lupus erythematosus (SLE) and as markers of disease activity. METHODS: We included 73 consecutive patients (62 female) with SLE (four or more ACR criteria) of recent onset (<1 yr since diagnosis). As control groups we included 130 healthy blood donors and 261 patients with 11 systemic autoimmune diseases (SAD). Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). A venous blood sample was drawn to measure three anti-chromatin antibodies [anti-nucleosome (anti-NCS), anti-double-stranded DNA (anti-dsDNA) and anti-histones (anti-HST)] by enzyme-linked immunosorbent assay. RESULTS: The prevalence of anti-chromatin antibodies in SLE patients and healthy controls was 100 and 3% respectively for anti-NCS, 63 and 5% for anti-dsDNA, and 15 and 3% for anti-HST. Anti-NCS had a sensitivity of 100% and specificity of 97% for SLE diagnosis. When SLE and SAD patients were compared [excluding mixed connective tissue disease (MCTD)], the sensitivity of anti-NCS, anti-dsDNA and anti-HST antibodies for SLE diagnosis was 93, 71 and 40% respectively and the specificity was 97, 98 and 98%. Anti-chromatin antibodies were not useful in differentiating between SLE and MCTD patients. Anti-NCS antibodies showed the highest correlation with disease activity (r = 0.45, P < 0.0001), especially in patients negative for anti-dsDNA antibodies (r = 0.58, P = 0.001). Anti-NCS antibodies also showed strong association with renal damage (odds ratio 4.1, 95% confidence interval 1.2-13.6, P = 0.01). CONCLUSION: Anti-NCS antibodies could be a useful tool in the diagnosis and assessment of disease activity in SLE patients, especially in patients who are negative for anti-dsDNA antibodies.     

Nonrenal and renal activity of systemic lupus erythematosus: a comparison of two anti-C1q and five anti-dsDNA assays and complement C3 and C4

Associations of different assays for antibodies to C1q (anti-C1q) and to dsDNA (anti-dsDNA) and of complements C3 and C4 with disease activity in patients with systemic lupus erythematosus (SLE) were studied. The clinical manifestations of 223 SLE patients were recorded, and the disease activity was assessed by the SLEDAI score. Anti-C1q were determined by two enzyme-linked immunosorbent assays (ELISA) and anti-dsDNA by a radioimmunoassay (RIA), a Crithidia immunofluorescence (IF) assay and three ELISA assays using human telomere DNA, plasmid DNA circles, or calf thymus DNA as antigens, respectively. Complement C3 and C4 were determined by nephelometry. Control sera were obtained from 98 blood donors. In patients with SLE, the prevalence of anti-C1q was 17–18% and that of anti-dsDNA was 36–69%. Anti-C1q, anti-dsDNA, and complement C3 and C4 correlated well with the overall activity of SLE (r?=?0.323–0.351, 0.353–0.566, and ?0.372–0.444, respectively; P?<?0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for active lupus nephritis among SLE patients were 40–44, 92, 29, and 91–92% for anti-C1q and 48–68, 29–66, 11–16, and 86–91% for anti-dsDNA, respectively. Patients with active nephritis had higher levels of anti-C1q and lower levels of C3 and C4 than patients with inactive nephritis (P?=?0.003–0.018). The corresponding associations of anti-dsDNA were somewhat weaker (P?=?0.023–0.198). Hematological parameters reflecting disease activity correlated clearly better with anti-dsDNA and complement C3 and C4 than with anti-C1q. Anti-C1q is inferior to anti-dsDNA as a diagnostic test in SLE and in the evaluation of overall clinical activity of the disease. Anti-C1q together with complement C3 and C4 may offer useful additional information to monitor lupus nephritis activity. There are no practical differences between different assays for anti-C1q and anti-dsDNA.     

Autoantibodies to lipoprotein lipase and dyslipidemia in systemic lupus erythematosus

OBJECTIVE: To demonstrate the binding of bovine lipoprotein lipase (LPL) by IgG from sera obtained from patients with systemic lupus erythematosus (SLE) and other rheumatic diseases, and the relationship of anti-LPL to triglyceride levels in SLE. METHOD: Binding of LPL by IgG from sera obtained from patients with SLE and other rheumatic diseases was measured by an enzyme-linked immunosorbent assay technique. Lipid profiles for fasting blood samples obtained from SLE patients and control subjects were determined. RESULTS: Sera obtained from 105 patients with SLE were assessed for reactivity with LPL, and 49 (47%) of the results were positive. Sera obtained from patients with rheumatoid arthritis (RA) (n = 80), Sj?gren's syndrome (n = 30), polymyositis and dermatomyositis (n = 30), and progressive systemic sclerosis (n = 31) were also studied, and 10 (13%), 3 (10%), 12 (40%), and 13 (42%), respectively, were positive for reactivity with LPL. It was determined that all affinity-purified anti-double-stranded DNA (dsDNA) antibodies and 4 of 5 monoclonal anti-dsDNA antibodies bound to LPL. The binding of IgG depleted of anti-dsDNA to LPL indicates a second anti-LPL activity in SLE. Measurements of fasting lipid levels in SLE patients with anti-LPL revealed a strong positive correlation of antibody levels and total serum triglycerides, apolipoprotein B, and apolipoprotein E concentrations. CONCLUSION: Antibodies to LPL occurred in 47% of SLE patients and in a similar percentage of patients with polymyositis or systemic sclerosis. The prevalence of these antibodies was less in patients with RA or Sj?gren's syndrome. It is hypothesized that the elevated triglyceride levels in SLE patients are in part attributable to anti-LPL, and this lipid abnormality could contribute to the premature atherosclerosis known to be present in patients with SLE.     

Production and characterization of human monoclonal anti-idiotype antibodies to anti-dsDNA antibodies

Anti-dsDNA autoantibodies are the hallmark of systemic lupus erythematosus (SLE) and frequently correlate with disease activity. In this study we report the isolation and characterization of human anti-Id monoclonal antibody fragments as single-chain Fv fragments (scFv) against anti-dsDNA antibody. The anti-Id monoclonal antibodies, specific for anti-dsDNA antibodies, have been cloned from phage display antibody scFv libraries derived from a patient with SLE. The V gene repertoires were derived from the RNA obtained from the B cells of an SLE patient with anti-Ro/SSA and anti-La/SSB antibodies. Affinity-purified anti-dsDNA antibodies were used for selection of bacterial clones producing specific scFv antibody fragments against anti-dsDNA antibodies and little reactivity with normal IgG and other IgG antibodies by ELISA. The anti-Id antibody recognizes a public idiotope that is broadly cross-reactive with polyclonal and monoclonal anti-dsDNA antibodies. This binding was largely inhibited by dsDNA antigen. The anti-Id antibody inhibited anti-dsDNA binding to dsDNA antigen in immunoassays and in the Crithidia luciliae assay. The anti-Id scFv antibody fragments derived from human genes could modulate the pathogenicity of anti-dsDNA autoantibodies and may have therapeutic implications in SLE. They may also be used as probes in studies of the structure of the idiotype.     

An analysis of clinical disease activity and nephritis-associated serum autoantibody profiles in patients with systemic lupus erythematosus: a cross-sectional study.

OBJECTIVE: To establish the correlation between lupus nephritis-associated autoantibody levels and the presence/activity of lupus nephritis and global disease activity using cross-sectional data in patients with systemic lupus erythematosus (SLE). METHODS: Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index. Antibody levels against single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), histones, nucleosomes and heparan sulphate (HS) were analysed by ELISA in SLE patients with (n=11) and without (n=22) nephritis and in normal controls (n=21). Antibody subclasses were also analysed. RESULTS: Higher levels of anti-dsDNA and anti-HS antibodies were found in patients with lupus nephritis, the level of anti-HS antibodies correlating with the BILAG renal score. Predominant subclasses were IgG1 and IgG3 for dsDNA antibodies, IgG2 for anti-nucleosome antibodies, and IgG2 and IgG3 for anti-HS antibodies. CONCLUSION: Correlation was demonstrated between antibodies to dsDNA, ssDNA, histones, nucleosomes and HS. There is a strong correlation between the level of anti-HS antibodies and disease activity in patients with lupus nephritis as measured by BILAG.     

The autoimmune response to chromatin antigens in systemic lupus erythematosus: autoantibodies against histone H1 are a highly specific marker for SLE associated with increased disease activity

This study investigates specificity, sensitivity and concomitant presence of antibodies against histone H1 (H1), nucleosomes (NUC), chromatin (CHR) and dsDNA in patients with systemic lupus erythematosus (SLE), analyses their association with SLE disease activity and characterizes the immunodominant epitope reactivity of anti-H1 antibodies and its relation to SLE disease activity. In a cross-sectional study 394 sera of patients with various rheumatic diseases and healthy subjects were analysed by ELISA for antibodies against H1, NUC, CHR and dsDNA. In addition, a longitudinal analysis was performed that included 121 sequential serum samples derived from 16 SLE patients to assess the relation of these antibodies as well as antibodies to histone H2B to SLE disease activity. To assess epitope reactivity of anti-H1 antibodies overlapping synthetic peptides covering the entire H1 sequence were used. Anti-H1 antibodies yielded a sensitivity of approximately 45% and a specificity of over 98% for SLE, which was comparable to that found for anti-dsDNA antibodies. Anti-CHR and anti-NUC antibodies were of similar sensitivity but slightly (anti-CHR) or considerably (anti-NUC) less specific for SLE (95 and 85%, respectively). The sequential analysis revealed a strong correlation of anti-H1 antibodies with SLE disease activity that was better than the correlation of anti-dsDNA and anti-NUC antibodies, while only weak correlation was found for anti-CHR and anti-H2B antibodies. The immunodominant epitope for anti-HI was localised between amino acids 204 and 218 (pp204-218) and immune reactivity to this epitope also correlated with disease activity. Anti-H1 is a highly specific marker for SLE with a diagnostic value comparable to anti-dsDNA. A positive testing for anti-H1 indicates increased disease activity, as does the appearance of antibodies to its immunodominant epitope pp204-218.     

Utility of anti-Sm,anti-RNP,anti–Ro/SS-A,and anti–La/SS-B (extractable nuclear antigens) detected by enzyme-linked immunosorbent assay for the diagnosis of systemic lupus erythematosus

Objective. To determine the utility of anti-extractable nuclear antigen (anti-ENA) antibodies detected by enzyme-linked immunosorbent assay as a predictor for the diagnosis of systemic lupus erythematosus (SLE). Methods. Among 2,185 serum samples sent for testing for antinuclear antibodies (ANA) by indirect immunofluorescence, 259 consecutive patients with positive ANA were identified. Medical charts of these patients were reviewed to assess the clinical diagnosis, with the reviewer having no knowledge of the anti-ENA result. Clinical data were abstracted for all patients, and diagnoses established using American College of Rheumatology criteria. The utility of ENA antibodies in the diagnosis of SLE was determined by univariate and multivariate analysis among all patients who were positive for ANA, patients who were positive for ANA and for anti-double-stranded DNA (anti-dsDNA), and patients who were positive for ANA and negative for anti-dsDNA. Clinical differences between SLE patients with and those without anti-ENA antibodies were assessed. Results. Anti-ENA antibodies, especially anti-Ro/SS-A, showed strong predictive diagnostic value among ANA+/anti-dsDNA– patients, but were of no utility among ANA+/anti-dsDNA+ patients. The only clinical manifestations that were more common among anti-ENA+ SLE patients were pleuritis and the use of hydroxychloroquine. Conclusion. The presence of anti-ENA antibodies, especially anti-Ro/SS-A, is a useful predictor for the diagnosis of SLE, primarily among patients attending a referral rheumatology center who are positive for ANA and negative for anti-dsDNA. No major clinical differences were noted among ANA+ SLE patients with versus those without ENA.