Immunology of normal pregnancy and preeclampsia
Redman CWG., Sargent IL., Taylor RN.
© 2015 Elsevier Inc. All rights reserved. Preeclampsia develops in stages, only the last being the clinical illness. This is generated by a nonspecific, systemic (vascular), inflammatory response, secondary to placental oxidative stress and release of trophoblast-derived stress signals into the maternal circulation. The latter include factors that promote maternal endothelial dysfunction. Reactivity to fetal alloantigens appears not to be the direct cause of the overt clinical syndrome. However, maternal adaptation to fetal (paternal) alloantigens is crucial, particularly before and in the early stages after conception. A preconceptual phase involves maternal tolerization to paternal antigens in seminal plasma. After conception, regulatory T cells and decidual NK cell recognition of fetal HLA-C on extravillous trophoblast may facilitate placental growth by immunoregulation. Complete failure of this mechanism would cause miscarriage, while partial failure would cause poor placentation and dysfunctional uteroplacental perfusion, which is the early symptomless phase of preeclampsia. The first-pregnancy preponderance and partner specificity of preeclampsia can be explained by this model. In preeclampsia, the balance of circulating T helper cells is shifted from the Th2 bias of normal pregnancy, towards Th1 and Th17. Th17 promotes autoimmunity. Agonistic autoantibodies to the angiotensin receptor-1 are a common but nonspecific feature of preeclampsia. They are likely to exacerbate maternal vascular inflammation, of which a late consequence is acute atherosis, affecting small uteroplacental spiral arteries. Acute atherosis shares features with both atherosclerosis and transplant vasculopathy, and may exacerbate malperfusion of the intervillous space. In summary, dysregulated maternal recognition of the alloimmune fetus appears to be important in the pathogenesis of poor placentation. The ensuing placental oxidative stress stimulates a global, maternal vascular inflammation, which is the end stage of the clinical disease.