Antibodies to cardiolipin in normal C57BL/6J mice: induction by estrogen but not dihydrotestosterone.
Autoantibodies against cardiolipin, a phospholipid, have been demonstrated in a variety of pathological states including several autoimmune conditions in humans and in certain lupus-prone mice. In this study we detected antibodies reactive to cardiolipin in normal C57BL/6J mice by ELISA. The autoantibodies are detected less frequently in the serum of male than in female mice, suggesting the influence of sex hormones. The relative refractoriness of normal male mice to the induction of anticardiolipin antibodies is not due to the suppressive effects of male hormones, since prepubertal orchiectomy has little influence on this autoantibody. Further, dihydrotestosterone treatment of orchiectomized mice has minimal effect on anticardiolipin antibodies. However, orchiectomized mice when given estrogen develop a marked increase in the incidence as well as the levels of these autoantibodies. Similarly, estrogen treatment of female mice further augments the incidence and the levels of these autoantibodies. Estrogen-treated mice also have antibodies reactive against other membrane phospholipids including phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The intensity of binding of autoantibodies to the above phospholipids varies among individual mice. To our knowledge, this is the first report on the demonstration of antiphospholipid autoantibodies in normal mice and induction of these antibodies by estrogen.