Personalized Medicine for Kidney Transplantation: Association of Graft Survival and Acute Transplant Rejection with Genetic Variation in B Cell Activating Factor System Signaling.

Kidney transplantation (KT) clinical outcomes are highly variable across patients and would benefit from predictive biomarkers to achieve personalized/precision medicine. The B cell activating factor (BAFF) system signaling plays an essential role in B lymphocytes' homeostasis, and is implicated in activation and survival of B lymphocytes. Single nucleotide polymorphisms (SNPs) in BAFF system genes are therefore strong candidates to identify the genetic mechanisms underpinning variable clinical outcomes in KT. We report here new findings on BAFF system genetic polymorphisms in KT patients in relation to two key phenotypes of clinical interest: graft survival and acute rejection (AR). A total of 168 KT patients, of which 29 suffered AR, participated in this study. The BAFF system polymorphisms in five genes TNFSF13B, TNFSF13, TNFRSF13C, TNFRSF13B, and TNFRSF17 were characterized using TaqMan SNP genotyping. Patients with KT who had an AA genotype in polymorphism rs3803800 of the TNFSF13 gene had a higher risk of suffering AR (p = 0.046; odds ratios = 3.38, 95% CI: 1.02-11.2). Moreover, patients with AA genotype (rs3803800) in the TNFSF13 gene had a significantly lower AR-free time than the GG/GA genotypes (69.2% vs. 85.7%; p = 0.037). Of importance, bioinformatics analysis showed that the polymorphism rs3803800 could alter splicing regulation and affect the proliferation-inducing ligand (APRIL) expression levels. The analysis of graft survival did not show a significant association with the polymorphisms analyzed in this study. In conclusion, the rs3803800 genetic polymorphism from this study of BAFF system genes appears to display importance in AR-free time for KT patients, and thus, warrants further research in independent populations as a putative predictive biomarker of AR. These findings also inform future personalized/precision medicine efforts and functional genomic studies in KT patients.