SERUM IL-35, PENTRAXIN-3, GALECTIN-3 AND HMGB1 IN RECURRENT PREGNANCY LOSS STRATIFIED BY CYTOMEGALOVIRUS SEROSTATUS: A CASE–CONTROL STUDY OF IRAQI WOMEN
DOI:
https://doi.org/10.61841/day57619Keywords:
recurrent pregnancy loss, cytomegalovirus, interleukin-35, pentraxin-3, galectin-3, HMGB1, maternal–fetal immune tolerance, IraqAbstract
Background: Recurrent pregnancy loss (RPL) affects roughsly 1–5% of couples, and in about half of cases the cause is never identified. Dysregulated maternal–fetal immune tolerance and chronic low-grade inflammation — to which latent infections such as cytomegalovirus (CMV) may contribute — are increasingly implicated. We compared four immuno-inflammatory biomarkers across RPL stratified by CMV serostatus.
Methods: In this case–control study, 210 women of reproductive age were recruited in Tikrit, Iraq (October 2023–September 2024) into three equal groups: parous controls without RPL, RPL with negative CMV serology (RPL CMV−), and RPL with positive CMV serology (RPL CMV+). Serum interleukin-35 (IL-35), pentraxin-3 (PTX-3), galectin-3 and high-mobility-group-box-1 (HMGB1), together with anti-CMV IgG/IgM and a routine laboratory panel, were measured by ELISA and automated analysers. Data were analysed with group comparisons, trend tests, correlation, receiver-operating-characteristic (ROC) analysis and Firth penalized logistic regression.
Results: IL-35 and galectin-3 decreased, whereas PTX-3 and HMGB1 increased, in a stepwise manner across control → RPL CMV− → RPL CMV+ (all P < 0.001, with significant monotonic trends). C-reactive protein and erythrocyte sedimentation rate rose in parallel. HMGB1 and PTX-3 separated RPL from controls with very high apparent accuracy (area under the curve ≈ 1.00), while IL-35 and galectin-3 were fair to good (0.77–0.88). In adjusted models, HMGB1 and PTX-3 were independently associated with CMV-positive RPL and higher galectin-3 with lower odds.
Conclusions: A coordinated shift toward a more pro-inflammatory, less tolerogenic serum profile was associated with RPL and was most marked in CMV-seropositive women. These cross-sectional associations are hypothesis-generating and require prospective external validation before any clinical application.
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