Gene signatures common to allograft rejection are associated with lymphocytic bronchitis. Issue 5 (27th March 2019) - Greenland, John R.
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.