Identification of HLA-antigens that modulate immunity to polyomavirus BK (BKV) infection could be used to (a) fine tune virus screening strategies in individual patients, and (b) facilitate discovery of MHC class I and class II binding peptides that can elicit clinically meaningful BKV specific immunity. Accordingly, we performed a retrospective study of 998 kidney transplant patients, in which clinical parameters and donor-recipient matching for specific HLA-antigens were examined in relation to occurrence of viremia. Emphasis was placed on matching frequency, rather than specific allelic frequencies, since a successful immune response requires sharing of HLA antigens between virus infected target and immune-effector cells. Using multivariate statistics, low risk of BK viremia and nephropathy, but not viruria, was associated with matching of HLA-A2 (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.29-0.87), HLA-B44 (HR 0.32, 95%CI 0.77-0.86) and HLA-DR15 (HR 0.35, 95%CI 0.08-0.93) (p<0.05), as well as male gender (HR 2.47, 95%CI 1.51-4.25, p<0001) and prior acute rejection (HR 1.64, 95%CI 1.04-2.55, p<0.05). In conclusion, HLA antigens that associated with a lower predisposition to development of BK viremia have been identified. Control of BK low grade BK viruria not complicated by viremia seems to require HLA-independent mechanisms.

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