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. Issue 10 (25th April 2017)

• Record Type: Journal Article
• Authors: 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.
• Other Names: Amico Patrizia investigator.; Aubert John‐David investigator.; Banz Vanessa investigator.; Beldi Guido investigator.; Benden Christian investigator.; Berger Christoph investigator.; Bochud Pierre‐Yves investigator.; Bucher Heiner investigator.; Bühler Leo investigator.; Carell Thierry investigator.; Catana Emmanuelle investigator.; Chalandon Yves investigator.; de Geest Sabina investigator.; de Rougemont Olivier investigator.; Dickenmann Michael investigator.; Duchosal Michel investigator.; Elkrief Laure investigator.; Fehr Thomas investigator.; Ferrari‐Lacraz Sylvie investigator.; Garzoni Christian investigator.; Soccal Paola Gasche investigator.; Gaudet Christophe investigator.; Giostra Emiliano investigator.; Halter Jörg investigator.; Heim Dominik investigator.; Hess Christoph investigator.; Hillinger Sven investigator.; Hofbauer Günther investigator.; Immer Franz investigator.; Klaghofer Richard investigator.; Laesser Bettina investigator.; Lehmann Roger investigator.; Lovis Christian investigator.; Marti Hans‐Peter investigator.; Martin Pierre Yves investigator.; Meylan Pascal investigator.; Mohacsi Paul investigator.; Morel Philippe investigator.; Mueller Ulrike investigator.; Mueller‐McKenna Helen investigator.; Müller Antonia investigator.; Müller Thomas investigator.; Müllhaupt Beat investigator.; Nadal David investigator.; Pascual Manuel investigator.; Passweg Jakob investigator.; Rick Juliane investigator.; Roosnek Eddy investigator.; Rosselet Anne investigator.; Rothlin Silvia investigator.; Ruschitzka Frank investigator.; Schanz Urs investigator.; Schnyder Aurelia investigator.; Seiler Christian investigator.; Stampf Susanne investigator.; Steiger Jürg investigator.; Stirnimann Guido investigator.; Toso Christian investigator.; Venetz Jean‐Pierre investigator.; Villard Jean investigator.; Wick Madeleine investigator.; Wilhelm Markus investigator.; Yerly Patrick investigator.;
• Is Part Of: American journal of transplantation. Volume 17:Issue 10(2017)
• Page Start: 2591
• Page End: 2600
• Publication Date: 2017-04-25
• Subjects: translational research/science -- infectious disease -- kidney transplantation/nephrology -- infection and infectious agents -- viral: BK/JC/polyoma -- T cell biology -- antigen presentation/recognition; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.14282
• Languages: English
• ISSNs: 1600-6135

Abstract

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. Abstract : Interferon‐γ ELISpot responses of CD8 T cells to immunodominant 9mer epitopes from the BK polyomavirus early viral gene region significantly increased in BK viremic patients but not in nonviremic controls, and are associated with viremia clearance posttransplantation, while standard 15mer T cell responses or antibody levels were uninformative.