Characterization of estrogen-induced autoantibodies to cardiolipin in non-autoimmune mice

Journal of Autoimmunity
D Verthelyi, S Ansar Ahmed

Abstract

Antibodies to cardiolipin, in humans, have been associated with a variety of autoimmune disorders including anti-phospholipid syndrome, systemic lupus erythematosus and Sjögren's syndrome. These antibodies have also been demonstrated in autoimmune-prone MRL-Mp-lpr/lpr (MRL/lpr), BXSB-Mp-(+yaa) (BXSB) and (NZW x BXSB)F1 mice. In previous work, we had shown that gonadectomized or intact male and female non-autoimmune C57BL/6 mice, upon treatment with estrogen, express autoantibodies to cardiolipin. In this study, we extend these findings and show that the expression of these antibodies persists for months even after the exposure to exogenous estrogen has been terminated. These antibodies are of IgM and IgG, but not IgA, isotypes, and the predominant IgG subisotype is IgG2b. Estrogen-induced antibodies to cardiolipin only minimally cross-reacted with DNA, actin or ovalbumin. The binding of antibodies to cardiolipin from autoimmune human patients in general has been shown to depend upon the presence of a cofactor, beta2-glycoprotein I. We found that in estrogen-treated C57BL/6 mice, as well as in SLE-prone MRL/lpr and BXSB mice, the binding of anti-cardiolipin antibodies to cardiolipin was not enhanced, but rather reduced, in the p...Continue Reading

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