NKG2C Natural Killer Cells in Bronchoalveolar Lavage Are Associated With Cytomegalovirus Viremia and Poor Outcomes in Lung Allograft Recipients

DOI Web Site 1 Citations
  • Daniel R. Calabrese
    Department of Medicine, University of California, San Francisco, CA.
  • Tiffany Chong
    Department of Medicine, University of California, San Francisco, CA.
  • Angelia Wang
    Department of Medicine, University of California, San Francisco, CA.
  • Jonathan P. Singer
    Department of Medicine, University of California, San Francisco, CA.
  • Marc Gottschall
    Department of Clinical Lab Immunology, University of California, San Francisco, CA.
  • Steven R. Hays
    Department of Medicine, University of California, San Francisco, CA.
  • Jeffrey A. Golden
    Department of Medicine, University of California, San Francisco, CA.
  • Jasleen Kukreja
    Department of Surgery, University of California, San Francisco, CA.
  • Lewis L. Lanier
    Department of Microbiology and Immunology and the Parker Institute for Cancer Immunotherapy, University of California, San Francisco, CA.
  • Qizhi Tang
    Department of Surgery, University of California, San Francisco, CA.
  • John R. Greenland

Description

<jats:sec> <jats:title>Background.</jats:title> <jats:p>Cytomegalovirus (CMV) infection is a risk factor for chronic lung allograft dysfunction (CLAD), which limits survival in lung allograft recipients. Natural killer (NK) cells that express the NKG2C receptor mediate CMV-specific immune responses. We hypothesized that NKG2C<jats:sup>+</jats:sup> NK cells responding to CMV in the lung allograft would reduce CMV-related inflammation and would improve CLAD-free survival.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods.</jats:title> <jats:p>We prospectively followed 130 subjects who underwent lung transplantation from 2012 to 2016. Bronchoalveolar lavage (BAL) NK cells were immunophenotyped for NKG2C, maturation, and proliferation markers. CMV viral load, serologies, serial spirometry, and mortality were recorded from medical records. Natural killer cell subset association with CMV endpoints were made using generalized estimating equation-adjusted linear models. BAL NKG2C<jats:sup>+</jats:sup> NK cell association with CLAD-free survival was assessed by Cox proportional hazards modeling.</jats:p> </jats:sec> <jats:sec> <jats:title>Results.</jats:title> <jats:p>NKG2C<jats:sup>+</jats:sup> NK cells were more mature and proliferative than NKG2C<jats:sup>−</jats:sup> NK cells and represented a median of 7.8% of BAL NK cells. The NKG2C<jats:sup>+</jats:sup> NK cell proportion increased prior to the first detection of viremia and was nearly tripled in subjects with high level viremia (>1000 copies/mL) compared with no detected viremia. Subjects with increased BAL NKG2C<jats:sup>+</jats:sup> NK cells, relative to the median, had a significantly increased risk for CLAD or death (hazard ratio, 4.2; 95% confidence interval, 1.2–13.3).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions.</jats:title> <jats:p>The BAL NKG2C<jats:sup>+</jats:sup> NK cell proportion may be a relevant biomarker for assessing risk of CMV viremia and quantifying potential CMV-related graft injury that can lead to CLAD or death.</jats:p> </jats:sec>

Journal

  • Transplantation

    Transplantation 103 (3), 493-501, 2019-03

    Ovid Technologies (Wolters Kluwer Health)

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