(956) Dynamics of immune-checkpoint regulators and inflammatory cytokines associated with preterm birth before and after cerclage

A total of 64 women with CI comprised the study group, and 128 endocervical swab samples were collected before and after cervical cerclage. The participants were categorized into two groups based on disease severity, such as membrane bulging vs. non-bulging, and delivery outcomes, such as preterm vs. full-term delivery. Seventeen soluble ICRs and 17 inflammatory cytokines were quantified using the 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 were significantly decreased after cerclage compared to before (Figure 1). In contrast, TIM-3 and PD-L2 were increased, as well as twelve other cytokines. Pre-cerclage levels of CCL2/MCP-1, CXCL10/IP-10, GM-CSF, IL-1alpha, IL-6, IL-10, and IL-17A were significantly elevated in the preterm group compared to the full-term delivery group. Meanwhile, post-cerclage levels of LAG-3, CTLA-4, CD86/B7-2, and PD-L2 showed significantly decreased levels in patients with preterm delivery. Among those, pre-cerclage CCL2/MCP-1, GM-CSF, IL-1alpha, and IL-17A levels, and post-cerclage PD-L1 level showed significant association with preterm birth according to the univariate analysis (Figure 2). Pre-cerclage IL-17A (odds ratio = 2.3, 95% confidence interval = 1.3 to 5.2, and P-value = 0.014) was the most significant predictor in the finally selected model based on the multivariate analysis.

Conclusion:

Our study revealed the dynamic changes of ICRs and cytokines following cervical cerclage, and identified markers for preterm birth, including pre-cerclage IL-17A in patients with CI. By focusing on these components, our work contributes to a better understanding of the local immune landscape and supports the development of targeted strategies to improve pregnancy outcomes.