Specificity of Auto Antibodies to Histone H1 in SLE: Relationship to DNA-Binding Domains

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Abstract
Autoantibodies in the sera of patients with systemic lupus erythematosus were examined with respect to their specificity for proteolytic fragments of histone H1 that retain. or do not retain, DNA-binding domains. 16 of 31 sera contained IgG and IgM antibodies to histone HI. IgM antibodies to HI in 8 sera (50YO) were directed at 18kD and 20kD α -chymotrypic HI fragments that bore binding sites for DNA, as identified by staining immunoblots containing the fragments with ssDNA plus 6/0, a mouse monoclonal antibody against ssDNA. IgM with this type of histone HI specificity did not react with comparably-sized V8 protease fragments of HI. IgM antibodies to HI in the other patients were directed against entirely different epitopes which were preserved in V8 protease digests of HI. In serial studies of three patients during different phase of their SLE. the level of antibodies against the 18kD and ZOkD histone HI fragments varied in parallel with the level of anti-ssDNA antibodies in one and varied inversely in the other two. The data suggest that a significant proportion of autoantibodies to histone HI are directed at a limited number of epitopes localized to H1 fragments containing DNA-binding sites.