The role of interleukin-10 gene variants in inhibitor development in hemophilia: A meta-analysis

Background

A major therapeutic challenge in hemophilia is the development of inhibitors that neutralize replacement therapies. Interleukin-10 (IL-10), an anti-inflammatory cytokine, regulates immune responses and influences antibody production, suggesting a potential role in inhibitor formation.

Objectives

This systematic review aimed to investigate the association of IL-10 polymorphism with inhibitor formation in patients with hemophilia.

Methods

Following PRISMA guidelines, the study was registered in PROSPERO (CRD42024590045). Genetic studies on IL-10 polymorphisms and inhibitors were included, while case reports, reviews, and animal studies were excluded. A comprehensive search was conducted in PubMed and Scielo, covering records up to January 27, 2025. Methodological quality was assessed using Q-genie, and a meta-analysis was performed for polymorphisms with data from at least three studies, using the Mantel-Haenszel method.

Results

Of 105 screened studies, 19 were included in the systematic review and 12 in the meta-analysis. No significant association was found between IL-10 polymorphisms (rs1800896, rs1800871, rs1800872) and inhibitor formation. In a subgroup analysis, the T-rs1800871 and A-rs1800872 recessive models were associated with protection against inhibitor development in subjects with severe hemophilia A.

Conclusion

These findings suggest that IL-10 may not have a central role in the genetic predisposition to inhibitor formation. However, the significant association observed in the severe hemophilia A subgroup emphasizes the need for further investigation into the role of IL-10 in immune tolerance.