BK Viremia (BKV) and subsequent BK nephropathy are associated with renal graft loss. The Human Leukocyte Antigen (HLA) region has been implicated in susceptibility to viral infections such as hepatitis B, C, and HIV. In our study we hypothesize that the presence or absence of certain recipient HLA class II molecules increases the susceptibility to BKV in renal transplant recipients. We performed a retrospective, single center study of 433 patients who underwent renal transplant and had molecular genotyping for A, B, C, DR, DP and DQ alleles. Real-time quantitative PCR of BK virus DNA was performed on plasma of renal transplant recipients at 1, 6 and 12 months and with any unexplained rise in serum creatinine. Of 433 recipients, 57 had BKV. A statistically higher prevalence of BKV was noted in those with HLA DQ2, DQ3 and DQ4 versus HLA DQ5 and DQ6 (p-value of .028).

To determine functional significance we then synthesized BK Dunlop strain large T antigen (LTA) peptide PYHFKYHEKHFANAI (313-327), which has previously been shown to be an immunodominant BK peptide. Peptide binding to class II HLA multiplex beads was done. The peptide bound weakly to DQ alleles but bound strongly to certain DR alleles. While differences in HLA class II and BKV and LTA binding in the retrospective study and HLA multiplex beads assay, the clinical utility of these findings requires further study. Epitope analysis may elucidate whether a specific amino acid sequence rather than an allele-level difference may decrease the binding affinity of BK viral peptides and thus decrease T cell immune responsiveness in the setting of immunosuppression. This ideally will identify susceptible recipients who can be monitored more vigilantly to avoid over-immunosuppression.

CITATION INFORMATION: Shah P, Anderson K, Aubrey M, Roark C, Freed B, Wiseman A. HLA Class II and BK Virus Reactivation in Renal Transplant Recipients. Am J Transplant. 2016;16 (suppl 3).

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