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

Abstract

Background BK polyomavirus (BKPyV) DNAemia in renal transplant recipients increases risk of allograft failure, but BKPyVspecific 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