Mechanism of Human Chorionic Gonadotrophinmediated Immunomodulation in Pregnancy

Amolak S Bansal; Shabana A Bora; Srdjan Saso; J Richard Smith; Mark R Johnson; Meen-Yau Thum


Expert Rev Clin Immunol. 2012;8(8):747-753. 

In This Article

Thyroid Autoimmunity, hCG & the hCG/LH Receptor

It is well known for individuals with thyroid autoimmunity to have an increased rate of autoimmunity to other organs and vice versa.[51] This is particularly evident in autoimmune polyglandular endocrinopathy.[52] In women with thyroid autoimmunity, there is increased infertility and RM.[53] While the exact mechanism of this association is unclear, it is quite probably related to impaired Treg cell function, which promotes both autoimmunity and RM.[38] As such, it is possible that maternal anti-hCG autoantibodies may also be present in these women and reduce the functioning of this important hormone.

LH/hCG receptor is a member of rhodopsin/β(2) adrenergic receptor subfamily of G-protein-coupled receptors. It shares similarities with the receptor for FSH and thyroid-stimulating hormone (TSH) in having a glycosylated N-terminal domain, seven transmembrane domains and a C-terminal intracytoplasmic domain having a leucine-rich repeat section.[54] Using in situ hybridization and immunocytochemistry, Zhang et al. have demonstrated the expression of the LH/hCG receptor in term placenta as well as mid-luteal phase endometrium.[55]

It is now recognized that hCG has molecular similarity to TSH. This becomes clinically relevant in women with gestational trophoblastic disease with markedly raised levels of serum hCG, a small proportion of whom develop hyperthyroidism.[56] Anti-TSH receptor autoimmunity has long been recognized as a cause of hyperthyroidism. It is therefore not surprising that there should be autoimmunity directed against the LH/hCG receptor. The existence of crossreactivity between hCG and TSH and their corresponding receptors has been suggested by Toulis et al. to explain the increased frequency of first-trimester miscarriage in women with thyroid autoimmunity.[57] It is interesting that two decades earlier, Moncayo et al. observed women with either primary or secondary sterility with endometriosis to have anti-LH/hCG receptor antibodies.[58] These were detected using an ELISA technique and LH/hCG receptor isolated by affinity chromatography from bovine corpora lutea.