Multiple serologic reactions and their relationship to clinical activity in systemic lupus erythematosus

Isenberg, David; Shoenfeld, Yehuda; Schwartz, Robert S.

doi:10.1002/art.1780270203

Cited by 106 publications

(28 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In other studies no significant correlation between disease and anti-nDNA was found (50,51 ). Usually reactivity to individual histones has not been correlated with disease (45,52).…”

Section: Resultsmentioning

confidence: 84%

The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus.

Burlingame¹,

Ml²,

Starkebaum³

et al. 1994

J. Clin. Invest.

289

177

View full text Add to dashboard Cite

To gain insight into the mechanisms of autoantibody induction, sera from 40 patients with systemic lupus erythematosus (SLE) were tested by ELISAs for antibody binding to denatured individual histones, native histone-histone complexes, histone-DNA subnucleosome complexes, three forms of chromatin, and DNA. Whole chromatin was the most reactive substrate, with 88% of the patients positive. By chi-square analysis, only the presence of anti-(H2A-H2B), anti-[(H2A-H2B) -DNA], and antichromatin were correlated with kidney disease measured by proteinuria > 0.5 g/d. SLE patients could be divided into two groups based on their antibody-binding pattern to the above substrates. Antibodies from about half of the patients reacted with chromatin and the (H2A-H2B) -DNA subnucleosome complex but displayed very low or no reactivity with native DNA or the (H3-H4)2-DNA subnucleosome complex. An additional third of the patients had antibody reactivity to chromatin, as well as to both subnucleosome structures and DNA. Strikingly, all sera that bound to any of the components of chromatin also bound to whole chromatin, and adsorption with chromatin removed 85-100% of reactivity to (H2A-H2B)-DNA, (H3-H4)2-DNA, and native DNA. Individual sera often bound to several different epitopes on chromatin, with some epitopes requiring quaternary protein-DNA interactions. These results are consistent with chromatin being a potent immunogenic stimulus in SLE. Taken together with previous studies, we suggest that antibody activity to the (H2A-H2B) -DNA component signals the initial breakdown of immune tolerance whereas responses to (H3-H4)2-DNA and native DNA reflect subsequent global loss of tolerance to chromatin. (J. Clin. Invest. 1994. 94:184-192.)

show abstract

“…In other studies no significant correlation between disease and anti-nDNA was found (50,51 ). Usually reactivity to individual histones has not been correlated with disease (45,52).…”

Section: Resultsmentioning

confidence: 84%

The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus.

Burlingame¹,

Ml²,

Starkebaum³

et al. 1994

J. Clin. Invest.

289

177

View full text Add to dashboard Cite

show abstract

“…In non-organ-specific autoimmune disorders, the best-documented case is the association of SLE with anti-dsDNA autoantibodies (26,27). A reduction in anti-dsDNA levels is indeed associated with remission of SLE, whereas an increase in anti-dsDNA may prompt a disease flare.…”

Section: Evolution Of Anti-srp Levels In Necrotizing Myopathymentioning

confidence: 99%

Correlation of anti-signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myopathy

Benveniste

Drouot

Jouen

et al. 2011

Arthritis & Rheumatism

195

132

View full text Add to dashboard Cite

Objective. Anti-signal recognition particle (anti-SRP) autoantibodies are associated with severe acquired necrotizing myopathies. The role of these autoantibodies remains elusive, and the evolution of anti-SRP levels over time is unknown. In this study, we developed an addressable laser bead immunoassay (ALBIA) technique to investigate a correlation between anti-SRP levels, serum creatine kinase (CK) levels, and muscle strength in patients with necrotizing myopathy.Methods. The diagnostic value of the ALBIA assay was determined by comparing serum levels of anti-SRP autoantibodies in 31 anti-SRP immunodotpositive patients to those in 190 healthy blood donors and 199 control patients with different inflammatory/ autoimmune conditions or polyclonal hypergammaglobulinemia. Among the 31 anti-SRP-positive patients, serum samples from 8 patients were monitored over time for levels of anti-SRP autoantibodies and levels of CK (determined at least 3 times, consecutively, over a mean followup period of 783 days). The relationship between levels of anti-SRP autoantibodies and levels of CK was tested using a linear mixed model.Results. The assay yielded positive results for anti-SRP in all anti-SRP immunodot-positive serum samples tested, while all control sera tested negative. The 8 anti-SRP-positive patients who were followed up longitudinally were found to have normalized CK levels and improved muscle strength. There was a striking correlation between the degree of myolysis, as measured by CK levels, in patients receiving therapy and the anti-SRP54 autoantibody levels in these same patients (P ‫؍‬ 0.002).Conclusion. Anti-SRP-positive myositis appears to be one of the few autoimmune diseases in which specific autoantibody levels are correlated with surrogate disease activity markers. These results reveal the usefulness of monitoring anti-SRP autoantibody levels in patients receiving therapy, and may also suggest a possible pathogenic role for anti-SRP autoantibodies in the necrotizing myopathies.Autoantibodies directed against signal recognition particles (anti-SRP) are present in a minority (4-6%) of patients with acquired inflammatory and/or necrotizing myopathies (1-5). Anti-SRP autoantibodies are generally associated with severe clinical forms of the disease, particularly those with heart and lung involvement (6,7) and resistance to steroid therapy (8-10).

show abstract

“…Twenty-seven of 33 disease exacerbations observed during the study period were accompanied by a positive test result for anti-dsDNA antibody (27 by the Farr assay, 19 by the C luciliae assay, and 23 by the ELISA). Twentyfour of these exacerbations were preceded by a significant increase in anti-dsDNA antibody levels (23 by the Farr assay, 12 by the C luciliae assay, and 17 by the ELISA). The first observance of a significant increase in anti-dsDNA antibody levels preceded the exacerbation by 8-10 weeks.…”

Section: Measurement Of Increases In As a Predictor Of Disease Exacermentioning

confidence: 99%

Measurement of increases in anti‐double‐stranded dna antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus

Borg

Horst

Hummel

et al. 1990

Arthritis & Rheumatism

510

227

View full text Add to dashboard Cite

To evaluate the predictive power of changes in levels of antibodies to double-stranded DNA (antidsDNA) as a predictor of disease exacerbations in systemic lupus erythematosus (SLE), we performed a prospective study on 72 unselected patients with SLE (mean duration of study 18.5 months, range 6-35 months). Patients were seen at least once every 3 months, and disease activity was scored according to a specific protocol. Plasma samples were obtained at least once every month and were assessed for anti-dsDNA antibody (by the Crifhidiu luciliue assay, an enzymelinked immunosorbent assay [ELISA], and the Farr assay) and for complement components C3 and C4. Twenty-seven of 33 disease exacerbations observed during the study period were accompanied by a positive test result for anti-dsDNA antibody (27 by the Farr assay, 19 by the C luciliae assay, and 23 by the ELISA). Twentyfour of these exacerbations were preceded by a significant increase in anti-dsDNA antibody levels (23 by the Farr assay, 12 by the C luciliae assay, and 17 by the ELISA). The first observance of a significant increase in anti-dsDNA antibody levels preceded the exacerbation by 8-10 weeks. Significant increases in anti-dsDNA antibody levels not followed by an exacerbation were observed in 5 cases by the Farr assay, in 7 cases by the C luciliue assay, and in 3 cases by the ELISA; however, in 3 cases, 2 cases, and 1 case, respectively, these increases were followed by an increase in disease activity that did not fulfill the criteria for an exacerbation. Serial measurement of anti-dsDNA antibody levels was more sensitive for predicting exacerbations than was measurement of C3 andor C4 levels (P < 0.03). Serial assessment of anti-dsDNA antibody levels, especially by the Farr assay, is a sensitive and reasonably specific method for predicting disease exacerbations in SLE.Systemic lupus erythematosus (SLE) is characterized by protean clinical manifestations and the occurrence of a variety of autoantibodies. Among these, anti-double-stranded DNA (anti-dsDNA) antibodies are highly specific for SLE and are detected at a high frequency (75-

show abstract

Multiple serologic reactions and their relationship to clinical activity in systemic lupus erythematosus

Cited by 106 publications

References 27 publications

The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus.

The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus.

Correlation of anti-signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myopathy

Measurement of increases in anti‐double‐stranded dna antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus

Contact Info

Product

Resources

About