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Multicenter Study
. 2022 Sep;22(9):2169-2179.
doi: 10.1111/ajt.17108. Epub 2022 Jun 15.

Plasma CXCL9 and CXCL10 at allograft injury predict chronic lung allograft dysfunction

Michael Y Shino  1 , Jamie L Todd  2 , Megan L Neely  2 , Jerry Kirchner  2 , Courtney W Frankel  2 , Laurie D Snyder  2 , Elizabeth N Pavlisko  2 , Gregory A Fishbein  1 , Joanna M Schaenman  1 , Kristen Mason  3 , Karen Kesler  3 , Tereza Martinu  4 , Lianne G Singer  4 , Wayne Tsuang  5 , Marie Budev  5 , Pali D Shah  6 , John M Reynolds  2 , Nikki Williams  7 , Mark A Robien  7 , Scott M Palmer  2 , S Sam Weigt  1 , John A Belperio  1
Affiliations
Multicenter Study

Plasma CXCL9 and CXCL10 at allograft injury predict chronic lung allograft dysfunction

Michael Y Shino et al. Am J Transplant. 2022 Sep.

Abstract

Histopathologic lung allograft injuries are putative harbingers for chronic lung allograft dysfunction (CLAD). However, the mechanisms responsible are not well understood. CXCL9 and CXCL10 are potent chemoattractants of mononuclear cells and potential propagators of allograft injury. We hypothesized that these chemokines would be quantifiable in plasma, and would associate with subsequent CLAD development. In this prospective multicenter study, we evaluated 721 plasma samples for CXCL9/CXCL10 levels from 184 participants at the time of transbronchial biopsies during their first-year post-transplantation. We determined the association between plasma chemokines, histopathologic injury, and CLAD risk using Cox proportional hazards models. We also evaluated CXCL9/CXCL10 levels in bronchoalveolar lavage (BAL) fluid and compared plasma to BAL with respect to CLAD risk. Plasma CXCL9/CXCL10 levels were elevated during the injury patterns associated with CLAD, acute rejection, and acute lung injury, with a dose-response relationship between chemokine levels and CLAD risk. Importantly, there were strong interactions between injury and plasma CXCL9/CXCL10, where histopathologic injury associated with CLAD only in the presence of elevated plasma chemokines. We observed similar associations and interactions with BAL CXCL9/CXCL10 levels. Elevated plasma CXCL9/CXCL10 during allograft injury may contribute to CLAD pathogenesis and has potential as a minimally invasive immune monitoring biomarker.

Keywords: cytokines/cytokine receptors; immunobiology; lung (allograft) function/dysfunction; lung failure/injury; lung transplantation/pulmonology; lung transplantation: living donor; pathology/histopathology; rejection: acute; translational research/science.

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Conflict of interest statement

Disclosure: The authors of this study have no conflicts of interest to disclose as described by the American Journal of Transplantation

Figures

figure 1:
figure 1:
Flow diagram of patient and sample size used in the analysis. BAL, bronchoalveolar lavage; LTR, lung transplant recipients.
See this image and copyright information in PMC

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