Presence of antinucleosome autoantibodies in a restricted set of connective tissue diseases - Antinucleosome antibodies of the IgG3 subclass are markers of renal pathogenicity in systemic lupus erythematosus

Objective. To study the frequency and disease specificity of antinucleosome antibody reactivity in diverse connective tissue diseases (CTD), and to de termine factors, such as antibody subclass, that may influence the pathogen icity of these antibodies in relation to disease activity. Methods. IgG and IgM antinucleosome activities on nucleosome core particles from 496 patients with 13 different CTD and 100 patients with hepatitis C were measured by enzyme-linked immunosorbent assay (ELISA). Of the patients with CTD, 120 had systemic lupus erythematosus (SLE), 37 had scleroderma ( systemic sclerosis; SSc), 20 had mixed connective tissue disease (MCTD), an d 319 had other CTD, including Sjogren's syndrome, inflammatory myopathy, r heumatoid arthritis, primary antiphospholipid syndrome, Wegener's granuloma tosis, Takayasu arteritis, giant cell arteritis, relapsing polychondritis, Behcet's syndrome, and sarcoidosis. Antinucleosome-positive sera were furth er analyzed, by isotype-specific ELISA, for antinucleosome and anti-double- stranded DNA (anti-dsDNA) IgG subclasses. Results. SLE, SSc, and MCTD were the only 3 CTD in which antinucleosome IgG were detected (71.7%, 45.9%, and 45.0% of patients, respectively). Antinuc leosomes of the IgG3 subclass were present at high levels in patients with active SLE and were virtually absent in those with SSc, MCTD, or inactive S LE, and their levels showed a positive correlation,vith SLE disease activit y. Of note, an increase in levels of anti-nucleosome of the IgG3 isotype wa s observed during SLE flares, and this increase was found to be closely ass ociated with active nephritis. Levels of anti-nucleosome of the IgG1 subcla ss showed a trend toward an inverse correlation,vith SLE disease activity. No significant fluctuation in the anti-dsDNA isotype profile was observed i n relation to SLE severity or clinical signs. Conclusion. Our data suggest that IgG anti-nucleosome is a new marker that may help in the differential diagnosis of CTD; anti-nucleosome of the IgG3 isotype might constitute a selective biologic marker of active SLE, in part icular, of lupus nephritis.