Immunity, thyroid function and pregnancy: molecular mechanisms.
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 (T(REG)) cells is key to this maintenance. T(REG) 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 T(REG) cells, which is caused by the rapid fall in the numbers of these cells after delivery.
Weetman
Anthony P
AP
Department of Human Metabolism, Faculty of Medicine, Dentistry and Health, University of Sheffield, The Medical School, Beech Hill Road, Sheffield S10 2RX, UK. a.p.weetman@sheffield.ac.uk
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000378:metabolism / Q000503:physiopathology*; D015551:Autoimmunity; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006649:Histocompatibility Antigens / Q000097:blood; D006801:Humans; D007108:Immune Tolerance; D010920:Placenta / Q000276:immunology; D049590:Postpartum Period; D011247:Pregnancy / Q000276:immunology*; D011644:Puerperal Disorders / Q000378:metabolism / Q000503:physiopathology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D013959:Thyroid Diseases / Q000378:metabolism / Q000503:physiopathology*; D013961:Thyroid Gland / Q000503:physiopathology*
D001323:Autoantibodies; D016207:Cytokines; D006649:Histocompatibility Antigens