Epithelial cell death markers in bronchoalveolar lavage correlate with chronic lung allograft dysfunction subtypes and survival in lung transplant recipients—a single-center retrospective cohort study

Liran Levy, Alexander Tigert, Ella Huszti, Tomohito Saito, Nicholas Mitsakakis, Sajad Moshkelgosha, Betty Joe, Kristen M. Boonstra, Jussi M. Tikkanen, Shaf Keshavjee, Stephen C. Juvet, Tereza Martinu

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic lung allograft dysfunction (CLAD) remains the leading cause of late death after lung transplantation. Epithelial injury is thought to be a key event in the pathogenesis of CLAD. M30 and M65 are fragments of cytokeratin-18 released specifically during epithelial cell apoptosis and total cell death, respectively. We investigated whether M30 and M65 levels in bronchoalveolar lavage (BAL) correlate with CLAD subtypes: restrictive allograft syndrome (RAS) versus bronchiolitis obliterans syndrome (BOS). BALs were obtained from 26 patients with established CLAD (10 RAS, 16 BOS) and 19 long-term CLAD-free controls. Samples with concurrent infection or acute rejection were excluded. Protein levels were measured by ELISA. Variables were compared using Kruskal–Wallis, Mann–Whitney U test and Chi-squared tests. Association of M30 and M65 levels with post-CLAD survival was assessed using a Cox PH models. M65 levels were significantly higher in RAS compared to BOS and long-term CLAD-free controls and correlated with worse post-CLAD survival. Lung epithelial cell death is enhanced in patients with RAS. Detection of BAL M65 may be used to differentiate CLAD subtypes and as a prognostic marker in patients with established CLAD. Understanding the role of epithelial cell death in CLAD pathogenesis may help identify new therapeutic targets to improve outcome.

Original languageEnglish
Pages (from-to)965-973
Number of pages9
JournalTransplant International
Volume32
Issue number9
DOIs
StatePublished - 1 Sep 2019
Externally publishedYes

Keywords

  • M30
  • M65
  • bronchoalveolar lavage
  • epithelial cell death
  • lung transplant
  • survival

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