BK polyomavirus-specific 9mer CD8 T-cell responses correlate with clearance of BK viremia in kidney transplant recipients: First report from the Swiss Transplant Cohort Study (STCS).

Leboeuf, Céline; Wilk, Sabrina; Achermann, Rita; Binet, Isabelle; Golshayan, Dela; Hadaya, Karin; Hirzel, Cédric; Hoffmann, Matthias; Huynh-Do, Uyen; Koller, Michael T; Manuel, Oriol; Mueller, Nicolas J; Mueller, Thomas F; Schaub, Stefan; van Delden, Christian; Weissbach, Fabian H; Beldi, Guido; Banz Wüthrich, Vanessa; Stirnimann, Guido; Hirsch, Hans H; ... (2017). BK polyomavirus-specific 9mer CD8 T-cell responses correlate with clearance of BK viremia in kidney transplant recipients: First report from the Swiss Transplant Cohort Study (STCS). American journal of transplantation, 17(10), pp. 2591-2600. Wiley-Blackwell 10.1111/ajt.14282

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BK polyomavirus (BKPyV) causes premature kidney transplant (KT) failure in 1-15% of patients. Since antivirals are lacking, most programs screen for BKPyV-viremia and, if positive, reduce immunosuppression. To evaluate the relationship of viremia and BKPyV-specific immunity, we examined prospectively cryopreserved plasma and PBMCs at T0, T6, and T12 months post-transplant from 28 viremic KT patients and 68 non-viremic controls matched for the transplantation period. BKPyV-IgG seroprevalence was comparable between cases (89.3%) and controls (91.2%;p=0.8635), but cases had lower antibody levels (p=0.022) at T0. Antibody levels increased at T6 and T12, but were not correlated with viremia clearance. BKPyV-specific T-cell responses to pools of overlapping 15mers (15mP) or immunodominant CD8 9mers (9mP) from the early viral gene region were not different between cases and controls at T0. However, clearance of viremia was associated with stronger 9mP-responses at T6 (p=0.042) and T12 (p=0.048), whereas 15mP-responses were not informative (T6 p=0.359; T12 p=0.856). BKPyV-specific T-cells could be expanded in vitro from all patients post-transplant permitting identification of 78 immunodominant 9mer-epitopes including 50 new ones across different HLA-classI. Thus, 9mP-responses may be a novel marker of reconstituting CD8 T-cell function that warrant further study as complement of plasma BKPyV-loads for guiding immunosuppression reduction. This article is protected by copyright. All rights reserved.

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