Anti-histone antibodies in the serum of autoimmune MRL and NZB NZW1 F1 mice

Anti-histone antibodies have been reported in a number of human autoimmune diseases, most notably idiopathic and drug-induced lupus erythematosus. In the current study, anti-histone antibody activity was detected using ELISA and electroblotting techniques in sera from autoimmune NZB W, MRL-lpr, and MRL-+/+ mice. Anti-histone activity increased with age, maturing earlier in females, in both NZB W and MRL-lpr mice. Testosterone treatment decreased anti-histone activity in NZB W mice and estrogen treatment from 2 weeks of age increased anti-histone activity in MRL-lpr mice, suggesting that gonadal hormones modified the expression of autoantibodies recognizing these protein antigens. Estrogen also increased serum IgG levels in MRL-lpr mice. Sex hormones affected expression of antibodies recognizing soy milk proteins but not ovalbumin in a similar manner. Nitrocellulose Western blots of SDS gels probed with sera from both types of autoimmune mice most often demonstrated reactivity with histone₁. Some mice, usually mature females, also recognized histone₄, histone₃, and histone₂.