title: Mechanism of human chorionic gonadotrophin-mediated immunomodulation in pregnancy.
abstract: Human chorionic gonadotrophin (hCG) is released within hours of fertilization and has a profound ability to downregulate maternal cellular immunity against trophoblastic paternal antigens. It also promotes angiogenic activity of the extravillous trophoblast, and impairment of this function may lead to inadequate placentation and an increased risk of preeclampsia. There is increasing evidence that hCG alters the activity of dendritic cells via an upregulation of indoleamine 2,3-dioxygenase activity. This reduces T-cell activation and cytokine production, as well as encouraging Treg cell recruitment to the fetal-maternal interface. These changes are critical in promoting maternal tolerance. hCG is also able to increase the proliferation of uterine natural killer cells, while reducing the activity of cytotoxic peripheral blood natural killer cells. There are rare reports of autoantibodies directed against hCG or the luteinizing hormone/hCG receptor in women with recurrent miscarriage. These autoantibodies are more frequent in women with thyroid autoimmunity. This may explain the association between thyroid autoimmunity and impaired fertility. Downregulating these anti-hCG and anti-luteinizing hormone/hCG receptor autoantibodies may be helpful in some women with early miscarriage or recurrent failed in vitro fertilization.
authors.affiliation: Department of Immunology and Allergy, St. Helier Hospital, Carshalton, Surrey, SM5 1AA, UK. amolak.bansal@esth.nhs.uk
authors.forename: Amolak S
authors.initials: AS
authors.lastname: Bansal
authors.forename: Shabana A
authors.initials: SA
authors.lastname: Bora
authors.forename: Srdjan
authors.initials: S
authors.lastname: Saso
authors.forename: J Richard
authors.initials: JR
authors.lastname: Smith
authors.forename: Mark R
authors.initials: MR
authors.lastname: Johnson
authors.forename: Meen-Yau
authors.initials: MY
authors.lastname: Thum
mesh_terms: D000026:Abortion, Habitual / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D006063:Chorionic Gonadotropin / Q000172:deficiency / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D056747:Immunomodulation; D008297:Male; D011247:Pregnancy; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D006063:Chorionic Gonadotropin; D006680:HLA Antigens