Maternal immunological aspects of pregnancy success and failure

Historically, auto- and alloimmune maternal immunological abnormalities have been proposed to account for pregnancy loss. However, most of these immunological theories have not fulfilled the criteria for causality. Autoimmunity involving antibodies to cardiolipin and possibly phosphatidylserine is the immunological factor best associated with recurrent abortion in a condition known as the antiphospholipid syndrome, which occurs in < 5% of women undergoing recurrent pregnancy losses. Dichotomous T helper cell 1 (Th1) and Th2 cytokine/growth factor responses to trophoblast or other antigens are proposed to be involved in pregnancy loss and success, respectively. According to this alloimmune theory, decidual immune and inflammatory cells secrete predominantly either Th1 or Th2 cell cytokines in response to the conceptus or other antigens. The Th1 cytokines tumour necrosis factor (TNF) and gamma-interferon are reported to affect many reproductive processes adversely, and the Th1 initiating cytokine interleukin 12 has been found in the decidua of aborting women with Th1 immunity to trophoblast. TNF polymorphisms or genes in linkage disequilibrium with TNF have also been associated with recurrent abortion in women with Th1 immunity to trophoblast. Further investigations are needed to define further the immunological mechanisms involved in pregnancy loss, so that effective therapies can be designed and properly studied.