Recent advances in understanding the clinical utility and underlying cause of antinucleosome (antichromatin) autoantibodies

The clinical utility of measuring antinucleosome autoantibodies (also known as antichromatin) in patients with systemic lupus erythematosus (SLE) has recently been evaluated by a number of different groups. Many studies found that antinucleosome autoantibodies were more prevalent than anti-DNA in SLE patients. In addition, antinucleosome autoantibodies were usually found to correlate with glomerulonephritis or disease activity better than anti-DNA in these patients. Antinucleosome autoantibodies are also found in patients with drug-induced lupus and Type I autoimmune hepatitis, but not usually in other diseases, thus showing good specificity for the above diseases. Several studies have shown that individuals with SLE have T cells reactive with nucleosomes and have increased levels of nucleosomes in their sera. The antinucleosome response in murine models of SLE is also T-cell–dependent and appears to be driven by self antigen. Nucleosome–antinucleosome immune complexes bind to glomeruli in vitro, and antinucleosome autoantibodies have been eluted from the kidneys of people and mice with glomerulonephritis. In one strain of mouse it was shown that antinucleosome autoantibodies were necessary, but not sufficient, to cause glomerulonephritis. These findings all show that antinucleosome autoantibodies are a sensitive and specific diagnostic marker for SLE and contribute to the pathology of glomerulonephritis.