P100 Resistance to BK Viremia in renal transplant patients is associated with HLA-DQ5 and HLA-DQ6

Abstract

Aim BK Viremia (BKV) and subsequent BK nephropathy are associated with renal graft loss. We hypothesized that the presence or absence of certain HLA allele(s) increases the susceptibility to BKV reactivation in renal transplant recipients on chronic immunosuppression. In a previous study, we compared 94 BKV+ patients and 682 normal bone marrow donors using our HLA Epitope Analysis Program that can detect every possible HLA epitope of 1–4 amino acids in the peptide-binding groove. The DQB1 epitope, EV—RGI84–90, (common to DQ5/6) was found to be significantly associated with resistance (p = 0.028). The HLA-DQB1 epitope, QLELRTT84–90, (common to DQ2/3/4) was associated with BK susceptibility (p = 0.02). Methods In this study, we used renal transplant patients who did not develop BKV as the controls to determine if HLA-DQ5/6 would remain associated with BKV resistance. Renal patients who had received a single transplant were analyzed for BKV and HLA-DQ typing. The typing of the recipient was used to separate the BKV+ and BKV− patients into three groups: homozygous for DQ5/6, heterozygous for DQ5/6 and DQ2/3/4 or homozygous for DQ2/3/4. Results Renal transplant recipients homozygous for DQ2/3/4 had a greater risk for disease than those homozygous for DQ5/6 (OR = 2.16 vs OR = 0.724). Patients who were heterozygous were also resistant to disease (OR = 0.508). The HLA typing of the donor was analyzed in the same manner but was not found to be significantly associated with BKV susceptibility. Conclusions The presence of a DQ5/6 allele is dominant resistant to BKV suggesting presentation of BK peptides on DQ5/6 to T cells may be required to prevent BK virus reactivation. Download : Download high-res image (99KB) Download : Download full-size image