Does the Immune System Induce Labor? Lessons from Preterm Deliveries in Women with Autoimmune Diseases

Abstract

A recent review of the literature suggested that thyroid autoimmunity is statistically associated with preterm delivery. This observation raises a number of follow-up questions, among them whether autoimmune function, in general, predisposes to premature delivery. A review of the English literature for the last 10 years, via PubMed search, finds strong supportive evidence for such a hypothesis. Since the fetal-placental unit represents a (semi) allograft within a maternal (allograft) recipient, it is reasonable to assume that it is subject to similar immunologic tolerance (and failure thereof) as solid organ transplants. As autoimmune responses represent a normal feature of tolerance failure in organ transplantation, similar autoimmune responses can also be expected with failure of tolerance of the fetal-maternal graft. The association of premature (and possibly also term) labor with autoimmune function may, therefore, be the consequence of abnormalities in normal fetal-placental tolerance, leading to uterine activation and labor.

Evidence for a Role for the Adaptive Immune Response in Human Term Parturition

“…The issue of whether the onset of labor represent ‘rejection’ of the semi-allograft has remained a speculation for decades. 68,106,107 …”

The impact of fetal gender on prematurity in dichorionic twin gestations after in vitro fertilization

“…Under the same concept the onset of labor is potentially viewed as the preprogrammed termination of immunologic tolerance of the fetal (semi)allograft at term, inducing uterine activation based on an immunological process akin to an acute GVHD [28]. Premature labor, under such a concept, would, of course, represent the premature termination of maternal tolerance of the fetal (semi)allograft.…”

Cutting edge assessment of the impact of autoimmunity on female reproductive success

“…Indeed, reversal of tolerance has been suggested as a potential labor-inducing event [11,36,37]. That the induction of labor may, indeed, be related to immunological processes, is supported by a number of recently published studies, investigating premature labor.…”

“…That the induction of labor may, indeed, be related to immunological processes, is supported by a number of recently published studies, investigating premature labor. For example, autoimmune diseases are, almost uniformly, associated with increased prematurity risk [36]. And twin pregnancies, involving a male offspring, have shorter pregnancies than twin pregnancies involving only female fetuses [38,39].…”