IFN-γ and IL-22 in premature ovarian insufficiency correlation with ovarian reserve markers and pathogenic implications: a cross-sectional study

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BACKGROUND: This case-control study aimed to investigate serum immunocytokine profiles and their clinical relevance in premature ovarian insufficiency (POI), with a particular focus on the potential of these cytokines as diagnostic biomarkers. METHODS: This case-control study investigated serum immunocytokine profiles in premature ovarian insufficiency (POI) using 28 patients and 17 controls from Guangxi Reproductive Hospital (2023-2024). Hormones (FSH, LH, E2, AMH, PRL, T) were measured by electrochemical luminescence and cytokines (IFN-γ, IL-1β, IL-6, IL-9, IL-17 A, IL-22, TGF-β1) by ELISA. RESULTS: POI patients exhibited higher FSH/LH and lower E2/AMH/PRL/T (all P < 0.05) versus controls, with increased menstrual irregularity (28.57% vs. 0%, P = 0.043). Distinct cytokine elevation occurred in IFN-γ and IL-22 (both P < 0.05), while other cytokines showed no differences. Menstrual regularity subgroups displayed comparable cytokine profiles despite divergent FSH/LH (P < 0.05), suggesting independent hypothalamic-pituitary-ovarian and immune dysregulation. IFN-γ/IL-22 positively correlated with FSH (r = 0.431/0.476) and POI status (r = 0.314/0.395), while inversely relating to AMH (r=-0.298/-0.345) and PRL (r=-0.382/-0.323) (all P < 0.05). ROC analysis demonstrated diagnostic potential: IFN-γ (AUC = 0.687, 95%CI:0.522-0.852, P = 0.037) and IL-22 (AUC = 0.735, 95%CI:0.574-0.897, P = 0.009). CONCLUSION: POI features a unique immunocytokine signature with elevated IFN-γ/IL-22 that correlates with ovarian reserve depletion and shows diagnostic promise. The dissociation between menstrual cyclicity and cytokine patterns implies distinct endocrine-immune pathophysiological mechanisms, positioning these cytokines as potential biomarkers for POI diagnosis and mechanistic research.