ArticleFrontiers in immunology2026
Dynamics of immune-checkpoint regulators and inflammatory cytokines and chemokines associated with preterm birth before and after cervical cerclage.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Cervical insufficiency (CI), characterized by painless cervical dilation during the second trimester, is a major cause of preterm birth. However, the local microenvironment associated with CI, particularly the roles of immune-checkpoint regulators (ICRs) and inflammatory cytokines and chemokines (ICKs), remains poorly understood. This study aimed to investigate the changes in ICRs and ICKs before and after cervical cerclage, as well as to identify predictors of preterm birth in patients with CI. Methods: A total of 64 women with CI comprised the study group, and 128 endocervical swab samples were collected before and after cervical cerclage. Participants were categorized according to disease severity, specifically, membrane bulging vs. non-bulging, and delivery outcomes, namely preterm vs. full-term delivery. Seventeen soluble ICRs and 17 ICKs were quantified using a Luminex multiplex assay. Results: Our results indicated significant differences in immunologic microenvironments before and after cerclage. Among ICRs, BTLA, CD28, GITR, and CD80 (B7-1) levels were significantly decreased after cerclage compared with pre-cerclage levels. In contrast, TIM-3 and PD-L2 were significantly increased, along with twelve other ICKs. Pre-cerclage ICRs and ICKs were generally higher in patients who received emergent cerclage with bulging membranes compared to those without bulging membranes. In particular, pre-cerclage levels of CCL2 (MCP-1), CXCL10 (IP-10), GM-CSF, IL-1α, IL-6, IL-10, and IL-17A were significantly elevated in patients who subsequently experienced preterm birth compared with those who delivered at term. Post-cerclage levels of LAG-3, CTLA-4, CD86 (B7-2), and PD-L2 were significantly lower in the preterm birth group. Among these, pre-cerclage IL-17A was the most significant predictor (odds ratio = 2.3) in the final multivariate model. The combination of pre-cerclage IL-17A and post-cerclage PD-L1 demonstrated excellent predictive performance, with an area under the receiver operating characteristic curve (AUC) of 0.901. Conclusion: Our study revealed the dynamic changes of ICKs and ICRs following cervical cerclage and identified key markers for preterm birth, including pre-cerclage IL-17A and post-cerclage PD-L1, in patients with CI. By focusing on these components, our work enhances the understanding of the local immune landscape and supports the development of targeted strategies to improve pregnancy outcomes.
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