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

Autoimmunity to hCG as a Mechanism of Impaired Fertility

As a means of contraception, the development of therapeutic antibody-mediated autoimmunity to hCG by vaccination has been reported for many years.[44,45] However, regular immunizations were required to maintain therapeutic anti-hCG antibody levels. Natural autoantibody reactivity against hCG was first demonstrated by Wass et al. in young women, but these were of insufficient avidity to be of clinically important.[46] Housseau et al. reported anti-hCG β-subunit antibodies in patients with bladder and germ cell tumors of the testis that secreted this protein.[47] Their later work confirmed the immunogenic region to be located within the central 20–65 amino acids of the hCG β-subunit. Amato et al. considered anti-hCG antibodies to be the cause of secondary infertility in a woman with regular menses and RM accompanied by persistently elevated hCG levels.[48] The autoantibody showed little crossreactivity with LH, and also α- and β-hCG. As such, it was considered to bind an area of spatial interaction between the latter hCG chains. Earlier work by Wang et al. noted nearly a quarter of 1020 women with primary or secondary infertility to have anti-hCG antibodies.[49] These declined significantly after three cycles of treatment with dexamethasone, vitamin C and vitamin D, with an improvement in the pregnancy rate. Subsequent work by Zou et al. noted that women with anti-hCG antibodies had an increased rate of miscarriage and lower rates of ongoing pregnancy than those without autoimmunity.[50] These rates were comparable with those seen in women with antiphospholipid and antitrophoblast antibodies.