- 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
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.