POLYMORPHISMS IN T-CELL RECEPTOR PATHWAY GENES AND INFECTION RISK IN KIDNEY TRANSPLANT RECIPIENTS

Introduction:

Infection remains a leading cause of morbidity and mortality in solid organ transplantation, influenced by genetic factors such as cytokine polymorphisms. Previous studies have associated genetic variations in genes like mannose-binding lectin, p53, toll-like receptor-4, and cytokines including TNF-α and β with increased infection risk. This study aimed to explore the relationship between T-cell receptor (TCR) pathway gene polymorphisms, CD3 T-cell counts, and infection risk in kidney transplant recipients.

Methods:

A cohort of 125 kidney transplant recipients was analyzed. Single nucleotide polymorphisms (SNPs) in genes involved in the TCR expression pathway were selected, including CD3 genes (CD3D, CD3E, CD3G), TCR α (TRA) and β (TRB) chain genes, PTPN22, ZAP-70, LCK, interleukin receptor pathway genes (IL2RA), and transcription factors regulating TCR gene expression (e.g., NFAT, AP-1). SNPs were identified using public databases such as dbSNP and the 1000 Genomes Project. Clinical data, including demographics, immunosuppressive regimens, and post-transplant outcomes, were collected. The incidence of infections within the first-year post-transplant was assessed retrospectively. Statistical analyses included Chi-square, Fisher’s exact test, Kruskal-Walli’s test, Dunn’s post-hoc test, Spearman correlation, multivariate linear regression, and Cox proportional hazards models.

Results:

Of the 125 patients, 60 experienced at least one infection episode within the first year after transplantation. Polymorphisms in PTPN22 (rs2476601) and IL2RA (rs7093069) were significantly associated with both CD3 counts and infection risk (p < 0.001). The C allele of PTPN22 was observed in 50% of the infected group compared to 23% of the non-infected group, while the T allele of IL2RA was found in 53% of the infected group versus 25% of the non-infected group. Spearman correlation analysis revealed a strong negative correlation between the presence of the C allele and CD3 counts (rs = −0.85, p < 0.001). Multivariate linear regression demonstrated that the PTPN22 and IL2RA genotypes significantly predicted CD3 counts (p < 0.001), independent of age, gender, donor type, and immunosuppressive therapy. Cox proportional hazards modeling confirmed that patients with the C allele of PTPN22 and T allele of IL2RA had a higher risk of infection (hazard ratio [HR] 2.50, 95% confidence interval [CI] 1.50–4.00, p = 0.001). Notably, a higher infection rate was observed among female patients (40% vs. 25%, p = 0.020). No significant differences were found between infected and non-infected groups concerning donor and recipient demographics or immunosuppressive protocols.

Conclusions:

Specific polymorphisms in TCR pathway genes, particularly PTPN22 and IL2RA, are significantly associated with lower CD3 T-cell counts and increased infection risk in kidney transplant recipients. Genetic screening for these polymorphisms could guide personalized immunosuppressive therapy, such as adjusting drug choice or dosing based on genotype, potentially reducing infection-related complications. However, this study’s limitations include its retrospective design, single-center nature, and relatively small sample size. Further research, including SNP screening in long-term healthy recipients, is underway to stratify infection risk more effectively. The observed gender differences in infection rates warrant further investigation to determine whether they reflect underlying biological differences or other factors.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.