IL‐17 Producing T to Foxp3+CD4+ Regulatory T Cell Ratio as a Diagnostic and Prognostic Marker in Women With Recurrent Pregnancy Loss and Its Implications for Intravenous Immunoglobulin Therapy

ABSTRACT Problem The imbalance in the Th17/Regulatory T (Treg) cell ratio is associated with recurrent pregnancy loss (RPL). This study aimed to determine a cut‐off for the Th17/Treg cell ratio to predict pregnancy outcomes in RPL and evaluate the effectiveness of intravenous immunoglobulin (IVIG) based on this cut‐off value. Method of Study This retrospective cohort study included 49 idiopathic RPL and 75 controls. The subgroups of IL‐17 + T cell to Foxp3 + T cell ratios in peripheral blood were measured using flow cytometry. The cut‐off values of Th17/Treg cell ratios were determined by the ROC curve to distinguish between RPL and controls. The IVIG treatment effectiveness in pregnancy outcome was compared between high‐ and low‐ratio groups. Pearson correlation assessed the Th17/Treg cell ratio's relationship with NK cell cytotoxicity (NKC), NK cell percentage, and Th1/Th2 cell ratio. Results Using the ROC curve, we identified six Th17/Treg cell ratio markers with diagnostic value, and the following two, CD3 + IL‐17 + T cell/CD3 + Foxp3 high T cell ratio (sensitivity at 97%) and CD4 + IL‐17 + T cell/CD3 + Foxp3 high T cell ratio (specificity at 93.61%), showed the highest statistical significance in diagnosing idiopathic RPL. Among the six diagnostic markers, in terms of predicting pregnancy outcomes with IVIG treatment, CD3 + IL‐17 + T cell/CD4 + Foxp3 + T cell ratio was the most valuable prognostic marker. In RPL women with high CD3 + IL‐17 + T cell/CD4 + Foxp3 + T cell ratio (≥ 1.096), the live birth rate (LBR) was improved with IVIG treatment. (IVIG treatment, 78.57% vs. no IVIG, 28.57%, p = 0.026). On the other hand, RPL women with low CD3 + IL‐17 + T cell/CD4 + Foxp3 + T cell ratio did not demonstrate the effectiveness of IVIG (LBRs with IVIG treatment, 50.00% vs. no IVIG, 84.62%, p = 0.219). In a correlation study, the CD3 + IL‐17 + T cell/CD4 + Foxp3 + T cell ratio was an independent prognostic marker, showing no correlation with NKC, NK cell percentage, and Th1/Th2 cell ratio. Conclusion The CD3 + IL‐17 + T/CD4 + Foxp3 + T cell ratio may serve as a valuable marker for understanding the pathogenesis of RPL, predicting pregnancy outcomes, and selecting candidates for immunotherapy. Our study demonstrates that IVIG treatment can significantly improve LBR in women with a high CD3 + IL‐17 + T/CD4 + Foxp3 + T ratio, offering a promising therapeutic approach for this challenging condition.