Abstract
Pregnancy and the postpartum period have a profound effect on autoimmune thyroid disease. Graves disease ameliorates during pregnancy, only to relapse postpartum, whereas postpartum thyroiditis is caused by destructive thyroiditis during the first few months after delivery. The immunology of pregnancy underlies these changes: the mother must maintain tolerance of the fetal semi-allograft while not suppressing her own immune system and exposing herself and the fetus to infection. Nonspecific factors, including hormonal changes, trophoblast expression of key immunomodulatory molecules and a switch to a predominantly T-helper-2-type pattern of cytokines, play some part in the maintenance of transient tolerance to paternal antigens in pregnancy; however, the generation of specific regulatory T (TREG) cells is key to this maintenance. TREG cells preferentially accumulate in the decidua but may also be present in the mother's circulation and are thus capable of regulating coincidental autoimmune responses through the phenomenon of linked suppression. In turn, this suppression may explain why thyroid autoantibody levels decline during pregnancy, which leads to remission of Graves disease. Postpartum exacerbation of autoimmunity may reflect an imbalance in TREG cells, which is caused by the rapid fall in the numbers of these cells after delivery.
Key Points
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Women are exposed to fetal alloantigens during pregnancy and must establish immunological tolerance to these antigens to prevent rejection of the fetus
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A generalized reduction of maternal immune responsiveness occurs during pregnancy, which is caused by increased levels of progesterone
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The trophoblast synthesizes a number of immunologically active molecules that suppress immune responses at the interface between mother and placenta
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Most importantly, the mother generates regulatory T (TREG) cells early in pregnancy that maintain a state of tolerance to fetal alloantigens as long as the pregnancy continues
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These TREG cells may ameliorate coincidental autoimmune thyroid diseases during pregnancy by linked suppression; worsening of these diseases postpartum may result from changes in the TREG cell and cytokine milieu
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Weetman, A. Immunity, thyroid function and pregnancy: molecular mechanisms. Nat Rev Endocrinol 6, 311–318 (2010). https://doi.org/10.1038/nrendo.2010.46
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DOI: https://doi.org/10.1038/nrendo.2010.46
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