Association between activating KIR and Perianal Crohn’s Disease in Pediatric Patients: A Nested case–control study

Objective : Perianal Crohn’s disease (PCD) is a severe complication of Crohn’s disease (CD) that significantly impacts the quality of life in pediatric patients. This study aims to investigate the clinical risk factors associated with PCD, particularly focusing on the role of Killer cell immunoglobulin-like receptor (KIR) gene present or not in a Canadian pediatric cohort. Methods : Data were collected from 1,021 individuals diagnosed with CD in Ottawa and Montreal, Canada. The study employed a cohort design to assess the association between KIR gene polymorphisms and the risk of developing PCD. Multivariable regression models were used to control for confounding variables such as age at diagnosis, gender, and disease location. The statistical analyses included descriptive statistics, propensity score matching, and inverse probability weighting to ensure robust results. Results : A total of 187 cases were analyzed, with 41 cases of PCD and 146 cases of non-perianal CD. The presence of KIR2DS5 was significantly associated with an increased risk of PCD (OR = 2.49, 95% CI: 1.09–5.69, P = 0.031) after adjusting for multiple covariates. Subgroup analyses revealed potential interaction effects based on ancestral origins, with French-ancestry children in Montreal showing a higher susceptibility to PCD when the activating KIR2DS5 present. Conclusion : The study demonstrates that KIR2DS5 is a significant genetic risk factor for PCD in pediatric patients. This finding highlights the importance of genetic factors in the pathogenesis of PD and suggests that KIR2DS5 genotyping could serve as a potential biomarker for identifying high-risk pediatric patients with CD. Future research should focus on validating these findings in larger and more diverse populations and exploring targeted therapies based on genetic profiles.