NATURALLY-OCCURRING AUTOANTIBODIES TO HUMAN CHORIONIC GONADOTROPIN AND ITS SUBUNITS IN OVARIAN CYST PATIENTS

Growing evidence supports the existence of immune-surveillance mechanisms in ovarian tumour patients, including autoantibodies to tumour associated and tumour specific antigens, tumour growth factors. Glycoprotein hormone human chorionic gonadotropin (hCG) and its hormone-specific hCGβ subunit have been associated with epithelial tumours such as bladder, lung, oral/facial, breast, cervical, ovarian, vaginal, prostate, renal and pancreatic carcinomas. It is believed that hCG plays a role of an autocrine growth factor for tumor cells. Here we have demonstrated that sera of patients with ovarian cyst contain naturally-occurring autoantibodies, predominantly of IgG2 isotype, that bind to hCG and its subunits with high affinity. Titration of blood sera from 36 female patients, aged 22-61 after ethical permission and informed consent, diagnosed with ovarian cyst and healthy age-matched controls (n=12) was performed using a classical enzyme-linked immunosorbent assay (ELISA). Binding of the sera to the following antigens was tested: hCGαβ, hCGβ, hCGα, hCGβ C-terminal peptide (hCGβCTP) and hCGβ core fragment (hCGβCF). The same type of ELISA (with necessary modifications) was used for further investigation of subclass usage and assessment of binding affinity of the detected autoantibodies. Our data indicates that the sera of the majority of patients with ovarian cyst contain significantly higher levels of the natural IgG antibodies binding to hCGαβ, hCGβ, hCGα, hCGβCTP and hCGβCF, than those of the healthy controls. Natural IgG antibodies to hCGαβ heterodimer were detected in 78% of cases, to hCGβ in 61% of cases, to hCGα in 78% of cases, to hCGβCTP in 69% of cases, to hCGβCF in 83% of cases. These autoantibodies predominantly belonged to the IgG2 subclass and were characterized by the high binding affinity. It is plausible that they cross- bind to sugar side chains of hCG and its subunits. Our data demonstrated that sera of patients with the ovarian cyst contains elevated levels of naturally-occurring IgG antibodies, which bind to hCG and/or its subunits. The overwhelming majority of these autoantibodies belong to the IgG2 isotype thus indicating that they might be directed against carbohydrate antigens within highly glycosylated hCG.