Autoantibodies in systemic lupus erythematosus.

Abstract

Cationic germ line gene-encoded anti-DNA antibodies appear to cause inflammatory lesions via deposition and in situ formation of immune complexes, but also perhaps through apoptosis of glomerular mesangial cells. Somatic mutation is not critical for the expression of the electrical net charge of anti-DNA. In one transgenic mouse model, the nephrogenicity of anti-DNA was dependent on the expression of interleukin alpha by epidermal cells. Anti-P autoantibodies are present in the serum of healthy children but are masked by IgG antibodies. Some anti-P antibodies appear to be a subset of antilymphocyte autoantibodies. It was confirmed that anti-Ro/SS-A antibodies react with structurally unrelated conformational epitopes. The combined results of immunofluorescence and enzyme-linked immunosorbent assay in the detection of antineutrophil cytoplasmic antibody has a 99.5% specificity for vasculitis among patients with connective tissue diseases. Antinucleosome antibodies are highly prevalent in patients with systemic lupus erythematosus and show an inverse correlation with nucleosome plasma levels. Transfected T-cell receptor alpha chains specific for nucleosomal autoepitopes from a Th clone that accelerates lupus nephritis, recognized the nucleosomal epitopes presented by antigen presenting cell-bearing 1-A molecules, as well as human DR molecules, via the classical major histocompatibility complex class II groove. IgG antibodies against (beta 2 -glycoprotein (GP)-1 are significantly associated with thrombosis in patients with antiphospholipid syndrome, with a specificity and sensitivity that ranges from 85% to 98% and 32% to 54%, respectively. The lupus anticoagulant activity, or the lack of it, of anti-beta 2-glycoprotein-1 appears to reside on the epitope specificity. Beta 2-glycoprotein-1 binds to apoptotic cells; in turn, anti-beta 2-glycoprotein-1 facilitate apoptotic cell clearance by macrophages. The recently described anti-A2/RA33 autoantibody appears to recognize an epitope capable of distinguishing patients with lupus or with rheumatoid arthritis from those with mixed connective tissue disease.