Immunoassay Used to Diagnose Polycystic Ovary Syndrome

Medical scientists at the University of Oklahoma (Norman, OK, USA) analyzed the serum of 32 patients with PCOS based on Rotterdam criteria and 38 age and body mass index (BMI) matched, ovulatory infertile women. These included seven diagnosed with Tubal Factor (TF), 12 Male Factor (MFI), and 19 unexplained infertile women. The team hypothesized that activating autoantibodies directed to the second extracellular loop (ECL2) of the gonadotropin releasing hormone receptor (GnRHR) could be present in PCOS patients and possibly be pathogenic and of diagnostic value. Such antibodies to other G protein receptors have been found to be significant in many disorders affecting predominantly women.

The scientists identified and synthesized the 28 AA hGnRHR ECL2 loop and used this epitope target for an ELISA assay. They found a significant increase in the developed ELISA optical density in subjects with PCOS (0.26±0.07) compared to subjects with TF (0.20±0.05), subjects with MFI (0.17±0.03), and subjects with unexplained infertility (0.17±0.03). These differences were maintained regardless of the BMI. This assay demonstrated a sensitivity of 91% and a specificity of 87% for PCOS.

The authors concluded that this autoantibody targeting the second ECL of the GnRHR at the hypothalamic/pituitary level will likely be causative of the abnormal cycling shown by PCOS subjects. The present assay, with validation from their ongoing activity and blocking studies, may represent the desired serological test needed to effectively screen subjects for possible PCOS.

David C. Kem, MD, the senior investigator, said, “We’d noticed that several female patients with postural orthostatic tachycardia syndrome (POTS) had autoantibodies that activate specific receptors called G-protein coupled receptors. It dawned on me that this type of autoantibody might also be present in PCOS patients, and the likely target for that would be receptors in the pituitary gland. We noticed in the course of our work that the autoantibodies connected to these receptors were using the second extracellular loop, a part of the receptor that sticks out from the cell wall into the serum.” The study was presented at the American Association of Clinical Endocrinologists’ 26th Annual Scientific & Clinical Congress held May 3-7, 2017, in Austin, Texas.

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