[Specificities and clinical significance of autoantibodies directed against histones].

ABSTRACT

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the occurrence of numerous autoantibodies directed against nuclear antigens. Anti-histone antibodies (AHA) are as prevalent as their anti-dsDNA counterparts in SLE. Despite their frequency and potential importance, there have not been given much attention to AHA until recently. Nucleosomes, the fundamental repeating units of the chromatin, are formed of complexes of histones and DNA. The nucleosome core particle is composed of a central tetramer of 2 molecules each of H3 and H4 flanked by 2 dimers of H2A and H2B and surrounded by 2 superhelical turns of approximately 146 base pairs of DNA. The full nucleosome contains a molecule of H1 located at the point where DNA enters and exits the nucleosome. Recent studies have shown that the post transcriptional modification of histone changes chromatin structure to regulate transcription and the concept of this mechanism "epigenetics" has become center of attention in the field of basic cell biology. There have been described diverging specificities of AHA. Many attempts to locate antigenic determinants recognized by AHA have been made and H1 and H2B have been thought as common targets in lupus patients. Studies on murine models of lupus have shown several interesting findings. The universal epitope is located on H2B in (NZBxNZW)F1 mice. In addition to core histones, MRL-MP/Fas(lpr) mice develop high titers of autoantibodies to H1. Autoimmunity to chromatin regularly involves humoral immune responses directed against H1. These histones appear to be an early (possibly initial trigger) autoantigen for this autoimmune response in lupus.