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Gene signatures common to allograft rejection are associated with lymphocytic bronchitis.

  • Author(s): Greenland, John R
  • Wang, Ping
  • Brotman, Joshua J
  • Ahuja, Rahul
  • Chong, Tiffany A
  • Kleinhenz, Mary Ellen
  • Leard, Lorriana E
  • Golden, Jeffrey A
  • Hays, Steven R
  • Kukreja, Jasleen
  • Singer, Jonathan P
  • Rajalingam, Raja
  • Jones, Kirk
  • Laszik, Zoltan G
  • Trivedi, Neil N
  • Greenland, Nancy Y
  • Blanc, Paul D
  • et al.

Published Web Location

https://doi.org/10.1111/ctr.13515
Abstract

Lymphocytic bronchitis (LB) precedes chronic lung allograft dysfunction. The relationships of LB (classified here as Endobronchial or E-grade rejection) to small airway (A- and B-grade) pathologies are unclear. We hypothesized that gene signatures common to allograft rejection would be present in LB. We studied LB in two partially overlapping lung transplant recipient cohorts: Cohort 1 included large airway brushes (6 LB cases and 18 post-transplant referents). Differential expression using DESeq2 was used for pathway analysis and to define an LB-associated metagene. In Cohort 2, eight biopsies for each pathology subtype were matched with pathology-free biopsies from the same subject (totaling 48 samples from 24 subjects). These biopsies were analyzed by multiplexed digital counting of immune transcripts. Metagene score differences were compared by paired t tests. Compared to referents in Cohort 1, LB demonstrated upregulation of allograft rejection pathways, and upregulated genes in these cases characterized an LB-associated metagene. We observed statistically increased expression in Cohort 2 for this LB-associated metagene and four other established allograft rejection metagenes in rejection vs paired non-rejection biopsies for both E-grade and A-grade subtypes, but not B-grade pathology. Gene expression-based categorization of allograft rejection may prove useful in monitoring lung allograft health.

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