Immunological aspects of pre-eclampsia

The first pregnancy preponderance and apparent partner specificity of pre-eclampsia suggest that it might have an immune aetiology. The pathogenesis of pre-eclampsia is undefined although it is clear that it is a placental disorder. The maternal syndrome appears to be mediated by placental ischaemia secondary to spiral artery insufficiency. This leads to a hypothesis that pre-eclampsia is a two-stage disease. The first comprises processes that limit the size of the spiral arteries (poor placentation) or obstruct them (acute atherosis). Either or both may have immunological causes although there is no direct evidence. Factors limiting placentation could involve maternal immune intolerance of the fetal allograft, which in their most extreme expression could lead to immunologically mediated abortion. Thus pre-eclampsia may be part of a wider spectrum of pregnancy loss secondary to poor maternal immune accommodation of her genetically disparate fetus. The second stage involves the consequences of the ensuing placental ischaemia. The syndrome is currently tentatively ascribed to diffuse maternal endothelial dysfunction. There is less reason to invoke immunological mechanisms in the second stage although neutrophil activation could explain generalized endothelial damage. It should be clear that these conclusions are provisional and that the greatest need is for more investigation to eliminate the uncertainty which clouds our concepts.