Association of TIM3 and LAG3 Gene Polymorphisms with Recurrent Miscarriage in HPV16-Infected Iraqi Women

Background: TIM3 and LAG3 regulate maternal-fetal immune tolerance by balancing Th1/Th2 responses, while polymorphisms in these genes may disrupt immunological homeostasis and increase the risk of miscarriage. The aim of this study is to investigate the association of TIM3 and LAG3 polymorphisms and HPV16 infection with Recurrent Miscarriage (RM) in Iraqi women. Methodology: This case-control study analyzed 230 placental tissues (130 RM patients and 100 healthy controls). HPV16-DNA was detected via PCR, and TIM3/LAG3 polymorphisms were identified using Sanger sequencing. Allele frequencies, genotype distributions, and statistical associations were evaluated using SPSS. Results: HPV16 was detected in 29.2% (38/130) of patients with RM versus 0% of controls (P=0.02). Novel TIM3 (accession numbers: LC870661–LC870663) and LAG3 (accession numbers: LC870664–LC870666) mutations were identified. The TIM3 A allele was significantly more frequent in RM patients (50% vs. 30%; P=0.03, OR=0.25, 95% CI:0.07–0.88). The LAG3 A allele frequency was higher in the patients (52.5% vs. 30%), but the difference was not statistically significant (P=0.10). Age and miscarriage frequency were not significantly correlated. Conclusions: TIM3 polymorphisms and HPV16 infection may contribute to recurrent miscarriages by disrupting immune tolerance.