Background & Objective: Recurrent Pregnancy Loss (RPL) has been associated with immunogenetic and inflammatory imbalances. Altered HLA-G expression and elevated levels of Interleukin-6 (IL-6) and C-Reactive Protein (CRP) may impair maternal-fetal tolerance, while the role of HLA-B27 remains unclear. This study evaluated HLA-G gene expression, HLA-B27, IL-6, and CRP in women with RPL. Materials & Methods: A case–control study was conducted among 240 women in Thiruvananthapuram, Kerala: 120 with RPL and 120 age-matched controls. Blood samples were analyzed for HLA-G gene expression (real-time PCR) and for IL-6, CRP, and HLA-B27 levels (ELISA). Statistical analysis was performed using Jamovi and Excel (P<0.05). Results: Women with RPL had significantly higher IL-6 and CRP levels and lower HLA-G protein and gene expression than controls. HLA-B27 showed no significant association with RPL. Logistic regression identified low HLA-G expression and elevated IL-6 as independent factors associated with RPL. ROC analysis indicated that CRP had the highest discriminatory ability, followed by HLA-G gene expression. Conclusion: Reduced HLA-G expression and heightened systemic inflammation are significantly associated with RPL. Combined immunogenetic and inflammatory markers may help identify women at risk and guide future therapeutic strategies.
Nadarajan et al. (2026) studied this question.