High prevalence of antibodies to histones among patients with primary biliary cirrhosis.

Histones are small, basic proteins involved in the packing of DNA into the eucaryotic nucleus. Using an immunodot assay and an enzyme-linked immunosorbent assay (ELISA), sera from patients with liver disease were tested for antibodies to the five individual histones H1, H2A, H2B, H3 and H4. Histones extracted from calf thymus and separated into individual fractions by gel exclusion chromatography were either immobilized on nitrocellulose or adsorbed to microtitre plates and the resulting immune complexes examined via a streptavidin-biotin bridge. Of the liver disease sera tested, only specimens obtained from primary biliary cirrhosis patients contained antibodies reactive with histones. The predominant reactivity was to histone H1 and H2B, and amounted to 74% for IgM antibodies, and 60% for IgG antibodies. Our data indicate that antibodies specific for histones might represent a novel serological marker for primary biliary cirrhosis.