Human leukocyte antigen-C*08 increases the risk of BK virus viremia in kidney transplant recipients

Abstract

BK virus (BKV) infection can cause graft loss in kidney transplant recipients. Several factors increase the risk of infection, including high level of immunosuppression, older age, and human leukocyte antigen (HLA) mismatch. The primary function of the major histocompatibility complex (HLA in human) is the presentation of peptides that originated from foreign or self-antigens to T cells to trigger an immune response, such as during infections. Identifying HLA genotypes that can influence the course of BKV infection could allow for stratifying patients according to their risk of developing the infection, thus personalizing the use of immunosuppressants. We conducted a retrospective study in a cohort of 1302 kidney transplant recipients, of whom 243 (19 %) developed BKV viremia. Clinical data and HLA genotype were evaluated for associations with BKV viremia. Among the 51 HLA genotypes analyzed, exploratory analysis revealed that patients expressing the HLA-C*08 genotype had a high risk of developing BKV viremia (p = 0.04). Using multivariate analyses adjusted for clinical variables that differed between patients with and without BK viremia (age and number of HLA-B mismatches), we confirmed that the HLA-C*08 genotype was associated with BK viremia. HLA-C*08, expressed by a sizeable proportion of the patients (82 individuals, or 6.3 % of the cohort), increased the risk of BKV viremia by 1.61 fold (p = 0.03). The HLA genotype may be useful in managing screening strategies for BKV in transplant recipients.