Preeclampsia: a view through the danger model

Classical thinking suggests that the immune system undergoes activation on the basis of discrimination between 'self' and 'non-self'. Accordingly, the fetus activates the mother's immune system because the fetus is in part 'non-self'. Thus, successful pregnancy depends on constraint of maternal immunity. Preeclampsia is an outcome of lost constraint. Instead, the danger model suggests that normal pregnancy, regardless of the expression of 'non-self' antigens, does not activate the maternal immune system unless that pregnancy expresses danger signals. Thus, preeclampsia stems from stress or abnormal cell death in pregnancy-related tissues. This compels expression of specific danger signals and potential activation of anti-fetal immunity, which secondarily feeds the syndrome. Study of preeclampsia from this perspective may bring forth novel mechanisms and indicators of vascular and metabolic dysfunction during pregnancy. (C) 2007 Elsevier Ireland Ltd. All rights reserved.