Immune Responses to BK Virus in Renal Transplant Recipients Receiving Intravenous Immunoglobulin Treatment.

BACKGROUND: BK polyomavirus (BKPyV) DNAemia in renal transplant recipients increases risk of allograft failure, but BKPyV-specific therapies are not available. While treatment with intravenous immunoglobulin (IVIG) has been reported, safety in a prospective randomized controlled setting is uncertain, and host immune response to BKPyV after IVIG is not well characterized.

METHODS: We investigated host immune responses to BKPyV in a multicenter, prospective, randomized, double-blinded, placebo-controlled pilot study of IVIG with protocolized immunosuppression reduction in adult kidney transplant recipients with BK DNAemia. Participants received 2 infusions of 1 g/kg up to 70 g each, 1 month apart, of IVIG or placebo and were followed for 1 year with adverse event monitoring. The primary endpoint was safety and tolerability of IVIG. Neutralizing antibody (nAb) to common BKPyV strains and BK-specific CD4+/CD8+ T-cell and natural killer cell responses were evaluated.

RESULTS: There were no adverse events. Forty percent of recipients in the treatment arm and 44.4% in the control arm cleared BK DNAemia at 3 months (relative risk, 0.90 [95% confidence interval, .23-2.89]). Overall, 80% of recipients with a sequenced BK genotype possessed cognate nAbs at baseline, and 100% acquired them by 3 months. Viral clearance was associated with higher percentages of BKPyV-specific CD8+ T cells prior to IVIG treatment (0.19% vs 3.01%; P < .01).

CONCLUSIONS: In this pilot study, treatment with 2 doses of IVIG was safe, but its impact on viral clearance is unclear. Control of DNAemia may depend upon intrinsic virus-specific host cellular and humoral response, but further studies are needed.

CLINICAL TRIALS REGISTRATION: NCT02659891.