Anti-histone antibodies in idiopathic and drug-induced lupus recognize distinct intrahistone regions.
We have identified regions within core histones that are antigenic for autoantibodies in systemic lupus erythematosus (SLE) and drug-induced lupus. An immunoblotting technique was used to determine the reactivity of lupus antibodies for intact histones and for trypsin-resistant histone fragments that lack the amino- and carboxyl-terminal amino acids that are normally exposed in native nucleosomes. In SLE, the predominant anti-histone response was restricted to epitopes in the trypsin-sensitive regions. Of 20 SLE sera that had strong antibody activity for multiple intact histones, 17 showed minimal activity with any of the corresponding trypsin-resistant fragments. A markedly different pattern of reactivity was present in sera of patients with procainamide (Pr)-induced lupus in which antibodies to H2A, H2B, and the H2A-H2B complex had strong fragment activity. Interestingly, recognition of trypsin-resistant fragments was also noted in a small number of SLE sera that contained antibodies to the H2A-H2B complex. In contrast to both SLE and Pr-induced lupus, antibodies induced by hydralazine (Hy) reacted primarily with H3 and H4. Furthermore, these antibodies bound equally well to the corresponding trypsin-resistant regions that are thought to be relatively unexposed in native nucleosomes. Thus, the specificities of anti-histone antibodies in SLE, Pr-induced lupus, and Hy-induced lupus are markedly different, but in each disease reactivity appears to be restricted to a limited number of histone determinants. The data raise the possibility that autoantigen in the form of native nucleosomes may be recognized in SLE and possibly in Pr-induced lupus. In contrast, the propensity of Hy to induce autoantibodies to determinants usually not recognized in SLE or Pr-induced lupus may suggest a different immunogenic stimulus in this disease.
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D000939:Epitopes; D006657:Histones / Q000276:immunology*; D006801:Humans; D006830:Hydralazine; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000276:immunology*; D046911:Macromolecular Substances; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D011342:Procainamide
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D006657:Histones; D046911:Macromolecular Substances; D010446:Peptide Fragments; D006830:Hydralazine; D011342:Procainamide