Association of PD-1 and CTLA-4 Gene Variants with Chronic Immune Thrombocytopenia in Pediatric and Adolescent Patients: A Cross-Sectional Study

Document Type : Original Article

Authors

Clinical and Chemical Pathology Department, Kasr Al AIny Hospitals, Cairo University, Cairo, Egypt.

Abstract

Despite the knowledge that complex dysregulation of the immune response is involved in the disease mechanism of chronic immune thrombocytopenia (cITP), the pathogenesis remains incompletely understood. The disruption of self-tolerance is one of the proposed underlying mechanisms of cITP. The cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4)/B7 and programmed death 1 (PD-1)/PD-L1 pathways inhibit T cell immunological function at different stages of T-cell activation, influencing immune regulation. Single nucleotide polymorphisms (SNPs) in PDCD1 and CTLA4 have been associated with susceptibility to specific autoimmune diseases. However, their association with chronic immune thrombocytopenia remains a topic of ongoing debate and uncertainty.
We aimed to explore PDCD1 and CTLA4 gene polymorphisms in cITP to clarify their role in disease pathogenesis and their potential association with progression to chronic disease.
Methods:
A retrospective cross sectional case control study was conducted where 48 cITP patients as well as 48 matched healthy controls were genotyped for PDCD1+ 7209, CTLA4 rs11571315 polymorphisms using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP).
Results:
Our study revealed a significant correlation between the heterozygous genotype (C/T), variant T allele of PDCD-1 +7209, and dual variant genotype with reduced platelet counts following therapy (p-value=0.037, 0.049, and 0.018).
Conclusion:
Our findings indicated that the T allele variant could potentially increase the incidence of chronic ITP, and that focusing on PDCD-1 may pave the way for innovative treatment strategies for patients with chronic ITP. Conversely, the CTLA4 rs11571315 SNP did not appear to influence susceptibility, chronicity, or severity in Egyptian children suffering from chronic ITP.

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