Background: The adaptive immune characteristics associated with BK Virus (BKV) infection and control remain incompletely described. In this study we further elucidate the immune response to BKV.

Methods: 29 patients undergoing renal transplantation from two institutions were followed prospectively for one year to evaluate the recipients' BKV specific humoral and cellular immune responses. ELISA assay detected IgG antibody titers against BKV strains 1 and 4 and intracellular staining for interferon gamma (IFN-γ) determined BKV-specific CD4⁺ and CD8⁺ T lymphocytes. We quantified T lymphocyte phenotypes and expression of activation and exhaustion markers to demonstrate lymphocyte functions.

Results: 4 patients developed BK viruria and 3 BK viremia. There were no clinical differences between BKV positive and negative patients. Viremic patients had an increase in BKV specific, IFN-γ producing CD8⁺ T Cells with time (P= 0.034). Prednisone was associated with fewer BKV specific CD8⁺ T Cells (P=0.027). Though there was a trend for viremic patients to have more IFN-γ producing CD4⁺ T cells, this did not reach significance. Viremic patients had an increase in IgG titers against both BKV 1 and 4(P= 0.044). Viremic patients also had higher titers against BKV 4 at 6 (P=0.035) and 12 months (P=0.004). A similar pattern was seen against BKV 1, but this did not reach significance. Viremic patients had fewer CD4⁺ central memory cells expressing activation markers CD38 (P=0.042) and HLA-DR (P= 0.027) at 1 month. Viremic patients had more CD8⁺ effector cells at baseline (P = 0.002) and 12 months (P = 0.009).

Conclusions: The response to BK viremia includes both a BKV specific humoral and cellular component, dominated by CD8⁺ T lymphocytes, and may be impaired by prednisone. Viremia was associated with fewer activated CD4⁺ central memory cells at 1 month, perhaps indicating an early memory deficit; and significantly more CD8⁺ effector cells at 12 months, potentially reflecting the cytotoxic response to viremia. Monitoring and modulating specific immune factors against BKV post kidney transplant could help identify risk of BKV infection and factors to harness as immunotherapy against BKV.

CITATION INFORMATION: DeWolfe D, Gandhi J, Mackenzie M, Broge T, Bord E, Mandelbrot D, Viscidi R, Cardarelli F, Pavlakis M, Tan C. Immune Response to BK Virus in Renal Transplant Recipients. Am J Transplant. 2016;16 (suppl 3).

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