The role of CTLA-4, epiregulin and PD-1 in women with polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is a hormonal, reproductive, metabolic disorder, affect female at reproductive age. PCOS is associated with hormonal and immunological defect, and chronic low-grade inflammation, that affect some proteins expression, like cytotoxic T Lymphocyte Associate protein 4 (CTLA-4), programmed death-1 (PD-1), epiregulin (EREG) in association with T-cell activation. These immunological parameters may indicate autoimmune diseases and PCOS. CTLA-4 and PD-1 are immune checkpoints that regulate the immunity during the chronic inflammation, by suppressing T-cells activation, natural killer cell, B-cell production. Epiregulin, a member of the epidermal growth factor (EGF) family, is released in response to luteinizing hormone(LH) released from granulosa cells in ovaries. There is an indirect link between PCOS and epiregulin in chronic low-grade inflammation. The purpose of this study was to indicate the role of CTLA-4, epiregulin, and PD-1 in women with polycystic ovarian syndrome, also the estimation of some related hormones level in PCOS, like prolactin, testosterone anti-Mullerian hormone (AMH). This study included 65 patients with PCOS and 56 normal controls (healthy women). Their average ages were from 20 to 45 years. The study subjects were from the private women's infertility clinics at the Medical City Hospital, Baghdad. The study lasted from November 2024 to January 2025. Metformin, vitamin D, and oral contraceptives were prescribed by consultant to patients. The blood samples were collected and CTLA-4, PD-1, EREG were measured by enzyme-linked immunosorbent assay (ELISA) technique. The results showed a significant decrease in CTLA-4 in patients (46.04 ±4.51) than in controls (70.46 ±9.41), (p≤0.01). Also, there was no difference in PD-1 level in patients (250.37 ±23.37), and controls (247.81 ±29.80), (p>0.05). EREG showed a significant increase in patients (1099.12 ±138.51), compared to controls (835.02 ±48.62), (p≤0.05). In addition, prolactin hormones recorded a significant increase in patients (154.86 ±27.22) compared to controls (13.91 ±1.50), (p≤0.05). While for the testosterone hormone there was a significant decrease in patients (16.36 ±2.58), as compared to controls (28.73 ±1.75), (p≤0.05). The AMH showed no difference between patients (5.79 ±0.40), and controls (4.18 ±0.44), (p>0.05). In conclusion, based on the current findings, the decrease in CTLA-4, and the increase in EREG in the patient’s group was associated with low-grade inflammation like PCOS.