Autoantibodies to nucleosomes and histone-DNA complexes

Individuals with systemic autoimmune diseases develop autoantibodies to nucleosome antigens. For many years, investigators have devoted much effort to precisely mapping epitopes on individual chromatin components. This approach, however, overlooks the existence of determinants that result from multimolecular interactions among nucleosome elements, such as DNA and histones. Anti-nucleosome antibodies can recognize a variety of complex epitopes and are especially prevalent in spontaneous and drug-induced lupus. Using numerous monoclonal anti-nucleosome antibodies obtained from autoimmune mice, we have further characterized these determinants and sequenced the variable region genes of these autoantibodies. I herein review these studies and their implications for the origin of antinuclear autoantibodies.