Evaluation of CD16, CD32, CD40, and CD152 polymorphisms in immune thrombocytopenia patients: a systematic review, meta-analysis, and trial sequential analysis.

BACKGROUND

Understanding the role of genetic polymorphisms in cluster of differentiation (CD)-related genes is crucial for elucidating susceptibility to immune thrombocytopenia (ITP). This study evaluates the polymorphisms of CD16, CD32, CD40, and CD152 in ITP patients through a systematic review, meta-analysis, and trial sequential analysis.

METHODS

A comprehensive literature review was conducted by a single investigator across multiple databases, including PubMed/Medline, Web of Science, Scopus, and Cochrane Library, up to 7 December 2025. The effect sizes were calculated using Review Manager 5.3 and presented as odds ratios (OR) with a 95% confidence interval. Analyses for publication bias, meta-regression, and sensitivity were performed using Comprehensive Meta-Analysis version 3.0.

RESULTS

Thirty-three articles were included in both qualitative and quantitative syntheses. Significant associations were found for the FcγRIIIA-158 F/V polymorphism across all genetic models, with the highest pooled OR of 2.61 in the homozygous model. No significant associations were observed for the FcγRIIA-131 H/R, FcγRIIB-232 I/T, CTLA-4 exon 1 A49G, CTLA-4 CT60, CD40 rs4810485 G > T, and CD40 rs1883832 C > T polymorphisms. The highest heterogeneity was noted in the heterozygous model for FcγRIIA-131 H/R (I2 = 69%), the allelic model for FcγRIIB-232 I/T (I2 = 60%), the allelic model for CTLA-4 exon 1 A49G (I2 = 43%), the dominant model for CTLA-4 CT60 (I2 = 80%), and the allelic model for CD40 rs1883832 C > T (I2 = 87%). The CD40 rs4810485 G > T polymorphism showed no heterogeneity (I2 = 0%) in most models.

CONCLUSION

The FcγRIIIA-158 F/V polymorphism is consistently associated with disease susceptibility across various genetic models. Other polymorphisms did not show significant associations, indicating the need for further research to validate these findings.