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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

C Leboeuf, S Wilk, R Achermann, Isabelle Binet, D Golshayan, K Hadaya, C Hirzel, Matthias Hoffmann, U Huynh-Do, M T Koller, O Manuel, N J Mueller, T F Mueller, S Schaub, C Van Delden, F H Weissbach, H H Hirsch & Swiss Transplant Cohort Study

abstract BK polyomavirus (BKPyV) causes premature kidney transplant (KT) failure in 1-15% of patients. Because 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 peripheral blood mononuclear cells at the time of transplantation (T0) and at 6 mo (T6) and 12 mo (T12) after transplant from 28 viremic KT patients and 68 nonviremic 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 (15mer peptide pool [15mP]) or immunodominant CD8 9mers (9mer peptide pool [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 after transplant, permitting identification of 78 immunodominant 9mer epitopes including 50 new ones across different HLA class I. Thus, 9mP-responses may be a novel marker of reconstituting CD8 T cell function that warrants further study as a complement of plasma BKPyV loads for guiding immunosuppression reduction.
   
citation Leboeuf C, Wilk S, Achermann R, Binet I, Golshayan D, Hadaya K, Hirzel C, Hoffmann M, Huynh-Do U, Koller M T, Manuel O, Mueller N J, Mueller T F, Schaub S, Van Delden C, Weissbach F H, Hirsch H H, Swiss Transplant Cohort Study . 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. Am J Transplant 2017; 17:2591-2600.
   
type journal paper/review (English)
date of publishing 25-04-2017
journal title Am J Transplant (17/10)
ISSN electronic 1600-6143
pages 2591-2600
PubMed 28326672
DOI 10.1111/ajt.14282