Genomics of BK viremia in kidney transplant recipients

Michelle Lubetzky, Yi Bao, Pilib Ó Broin, Kwaku Marfo, Maria Ajaimy, Aws Aljanabi, Graciela De Boccardo, Aaron Golden, Enver Akalin

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

BACKGROUND: This study aimed to investigate global gene expression profiles of BK viremia and nephropathy (BKVN) samples using microarrays to investigate the immunologic response to BK virus. METHODS: Patients were monitored for BK viremia in the blood monthly for 6 months, then at 9 and 12 months after kidney transplantation. BKVN and normal transplant kidney biopsy samples, and whole blood samples of patients with and without BK viremia were analyzed by Affymetrix Human Gene 1.0 ST Arrays. RESULTS: During a mean follow-up of 917±325 days, 61 of the 289 patients (21%) developed BK viremia at a median 149 (27, 1,113) days after transplantation with a median peak PCR titers of 35,900 (1,000, 2,677,000). The only significant risk factor for development of BK viremia was induction with anti-thymocyte globulin (P=0.03). Only four patients developed BKVN (1.3%). Pathogenesis-based transcript analysis revealed a significant increased expression of interferon-gamma and rejection induced (GRIT), quantitative cytotoxic T-cell (QCAT), quantitative constitutive and alternate macrophage, B-cell and natural killer cell-associated transcripts (NKAT), indicating an active inflammatory immune response in BKVN biopsies (n=3) compared to normal transplant kidney biopsies with (n=3) and without BK viremia (n=11). The whole blood gene expression profiles of 19 BK viremia patients revealed significant increased expression of GRIT, QCAT, and NKAT compared to 14 patients without viremia. CONCLUSIONS: The results showed increased activity of cytotoxic T cells and natural killer cells in BKVN and viremia samples resembling acute rejection and suggested the involvement of both adaptive and innate immunity.

Original languageEnglish (US)
Pages (from-to)451-456
Number of pages6
JournalTransplantation
Volume97
Issue number4
DOIs
StatePublished - Feb 27 2014

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Viremia
Genomics
Kidney
Natural Killer Cells
Biopsy
Transcriptome
Transplant Recipients
Active Immunity
BK Virus
T-Lymphocytes
Transplants
Antilymphocyte Serum
Adaptive Immunity
Innate Immunity
Kidney Transplantation
Interferon-gamma
B-Lymphocytes
Transplantation
Macrophages

Keywords

  • BK virus
  • Gene expression
  • Kidney transplantation
  • Microarrays
  • Polyoma nephropathy

ASJC Scopus subject areas

  • Transplantation

Cite this

Genomics of BK viremia in kidney transplant recipients. / Lubetzky, Michelle; Bao, Yi; Ó Broin, Pilib; Marfo, Kwaku; Ajaimy, Maria; Aljanabi, Aws; De Boccardo, Graciela; Golden, Aaron; Akalin, Enver.

In: Transplantation, Vol. 97, No. 4, 27.02.2014, p. 451-456.

Research output: Contribution to journalArticle

Lubetzky, M, Bao, Y, Ó Broin, P, Marfo, K, Ajaimy, M, Aljanabi, A, De Boccardo, G, Golden, A & Akalin, E 2014, 'Genomics of BK viremia in kidney transplant recipients', Transplantation, vol. 97, no. 4, pp. 451-456. https://doi.org/10.1097/01.TP.0000437432.35227.3e
Lubetzky M, Bao Y, Ó Broin P, Marfo K, Ajaimy M, Aljanabi A et al. Genomics of BK viremia in kidney transplant recipients. Transplantation. 2014 Feb 27;97(4):451-456. https://doi.org/10.1097/01.TP.0000437432.35227.3e
Lubetzky, Michelle ; Bao, Yi ; Ó Broin, Pilib ; Marfo, Kwaku ; Ajaimy, Maria ; Aljanabi, Aws ; De Boccardo, Graciela ; Golden, Aaron ; Akalin, Enver. / Genomics of BK viremia in kidney transplant recipients. In: Transplantation. 2014 ; Vol. 97, No. 4. pp. 451-456.
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AU - Bao, Yi

AU - Ó Broin, Pilib

AU - Marfo, Kwaku

AU - Ajaimy, Maria

AU - Aljanabi, Aws

AU - De Boccardo, Graciela

AU - Golden, Aaron

AU - Akalin, Enver

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AB - BACKGROUND: This study aimed to investigate global gene expression profiles of BK viremia and nephropathy (BKVN) samples using microarrays to investigate the immunologic response to BK virus. METHODS: Patients were monitored for BK viremia in the blood monthly for 6 months, then at 9 and 12 months after kidney transplantation. BKVN and normal transplant kidney biopsy samples, and whole blood samples of patients with and without BK viremia were analyzed by Affymetrix Human Gene 1.0 ST Arrays. RESULTS: During a mean follow-up of 917±325 days, 61 of the 289 patients (21%) developed BK viremia at a median 149 (27, 1,113) days after transplantation with a median peak PCR titers of 35,900 (1,000, 2,677,000). The only significant risk factor for development of BK viremia was induction with anti-thymocyte globulin (P=0.03). Only four patients developed BKVN (1.3%). Pathogenesis-based transcript analysis revealed a significant increased expression of interferon-gamma and rejection induced (GRIT), quantitative cytotoxic T-cell (QCAT), quantitative constitutive and alternate macrophage, B-cell and natural killer cell-associated transcripts (NKAT), indicating an active inflammatory immune response in BKVN biopsies (n=3) compared to normal transplant kidney biopsies with (n=3) and without BK viremia (n=11). The whole blood gene expression profiles of 19 BK viremia patients revealed significant increased expression of GRIT, QCAT, and NKAT compared to 14 patients without viremia. CONCLUSIONS: The results showed increased activity of cytotoxic T cells and natural killer cells in BKVN and viremia samples resembling acute rejection and suggested the involvement of both adaptive and innate immunity.

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KW - Microarrays

KW - Polyoma nephropathy

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