Autoimmunity: The Female Connection

The prevalence of autoimmune diseases in women may be the consequence of a bidirectional signaling network between hormones and the immune system that regulates female reproductive life. Two prototypical autoimmune diseases, rheumatoid arthritis and systemic lupus erythematosus, arise from 2 different immune responses that generate mutually exclusive signals in response to different inflammatory triggers. Certain estrogens may ameliorate the rheumatoid-arthritis-like TH1 response while exacerbating the lupus-like TH2 response. Studies of sex hormone metabolism in lupus patients reveal increased 16-hydroxylation of estrone in some patients and decreased levels of androgens as a result of increased oxidation at C17. These occurrences result in low serum levels of dehydroepiandrosterone (DHEA). Both the increase of 16-hydroxylation of estrone and the depletion of DHEA have immune effects that would tend to exacerbate a lupus-like TH2 response. This theoretical framework provides a rationale for ongoing initial clinical trials of exogenous hormones in autoimmune diseases.