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.
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.
Transplantation & Clinical Virology, Department Biomedicine, University of Basel, Basel, Switzerland.
C
C
Leboeuf
Transplantation & Clinical Virology, Department Biomedicine, University of Basel, Basel, Switzerland.
S
S
Wilk
Swiss Transplant Cohort Study, University Hospital Basel, Basel, Switzerland.
R
R
Achermann
Nephrology & Transplantation Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
I
I
Binet
Transplantation Center, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
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D
Golshayan
Service of Nephrology, University Hospitals Geneva, Geneva, Switzerland.
K
K
Hadaya
Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
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C
Hirzel
Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
M
M
Hoffmann
Division of Nephrology, Hypertension and Clinical Pharmacology, Inselspital Bern, Bern, Switzerland.
U
U
Huynh-Do
Basel Institute for Clinical Epidemiology and Biostatistics, Basel, Switzerland.
M T
MT
Koller
Infectious Diseases Service & Transplantation Center, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
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O
Manuel
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
N J
NJ
Mueller
Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
T F
TF
Mueller
Division of Transplant Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
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http://orcid.org/0000-0002-9170-1341
S
Schaub
Transplant Infectious Diseases Unit, University Hospitals Geneva, Geneva, Switzerland.
C
C
van Delden
Transplantation & Clinical Virology, Department Biomedicine, University of Basel, Basel, Switzerland.
F H
FH
Weissbach
Transplantation & Clinical Virology, Department Biomedicine, University of Basel, Basel, Switzerland.|Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
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HH
Hirsch
D000328:Adult; D000368:Aged; D001739:BK Virus / Q000302:isolation & purification / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D014766:Viremia
T cell biology; antigen presentation/recognition; infection and infectious agents; infectious disease; kidney transplantation/nephrology; translational research/science; viral: BK/JC/polyoma