Plasma CXCL9 and CXCL10 at allograft injury predict chronic lung allograft dysfunction.
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
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
revised:
24
05
2022
received:
16
02
2022
accepted:
26
05
2022
pubmed:
1
6
2022
medline:
1
9
2022
entrez:
31
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35634722
doi: 10.1111/ajt.17108
pmc: PMC9427677
mid: NIHMS1815611
pii: S1600-6135(22)29911-0
doi:
Substances chimiques
Biomarkers
0
CXCL10 protein, human
0
CXCL9 protein, human
0
Chemokine CXCL10
0
Chemokine CXCL9
0
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2169-2179Subventions
Organisme : NIAID NIH HHS
ID : UM2 AI117870
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI113315
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL108793
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL138256
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL112990
Pays : United States
Informations de copyright
© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.
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