Immunodystrophism: Evidence for a Novel Alloimmune Hypothesis for Recurrent Pregnancy Loss Involving Th1-Type Immunity to Trophoblast

ABSTRACT

Pregnancy loss is the most common complication of pregnancy. Recurrent pregnancy loss occurs in approximately 1% of pregnant women. Many immunologic theories have been proposed but have not withstood rigorous analysis. A novel alloimmune hypothesis involving T helper (Th) 1-type immunity to trophoblast is the latest theory proposed for recurrent pregnancy loss. The basic hypothesis is, in the decidua there are myriad of antigen presenting cells and other immune response cells. In response to trophoblast invasion, these cells may become activated. A by-product of this activation is the secretion by these cells of either a predominant Th1 or Th2 cytokine profile. In cases where a Th1 cytokine profile predominates, chiefly, interferon-gamma, tumor necrosis factor, or interleukin-12, these cytokines may directly or indirectly be detrimental to early placental cell differentiation and growth and toxic to embryo development. Further evidence for this novel hypothesis comes from recent findings of a genetic predisposition for a vigorous Th1 cytokine response in these women due to a polymorphism in the IL1B promoter region. Further studies are needed to substantiate definitive causative links between Th1-immunity to trophoblast and recurrent pregnancy loss. Clinical trials are also needed to determine the best therapy for this disorder.

KEYWORD

Trophoblast - T-helper 1-type immunity - recurrent pregnancy loss - immunodystropism

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