Abstract
A common response module (CRM) of 11 genes (BASP1, CD6, CD7, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, and TAP1) that define rejection across different transplanted organs has been defined previously. The CRM score quantifies injury and stratifies patients at increased risk of future fibrosis. We investigated if CRM could identify and distinguish phenotypes of rejection post lung transplantation.
We collected BAL fluid cell pellet at time of rejection diagnosis and explant tissues at redo-transplantation/autopsy (Bronchiolitis Obliterans Syndrome, BOS, n=13 vs. Restrictive allograft syndrome, RAS, n=17) and controls (unused donors for tissue; n=15 or BAL of stable patients (n=15)). Differential diagnosis was made using conventional criteria. RNA was extracted and the CRM gene expressions were measured using qPCR, normalized and compared.
CXCL9 (p=0.0025), CXCL10 (p=0.034) and ISG (p=0.007) were increased in RAS tissue vs. control. There were no differences in expression between BOS and control. The mean CRM score was higher in RAS versus control (p=0.028), but not different compared to BOS. Neither the CRM score nor individual gene expression levels in BAL were different compared to stable patients. No association between RNA in BAL and tissue was observed.
A proportion of the CRM genes were upregulated in RAS tissue compared to BOS and control. Since RAS shows typical interstitial inflammation/fibrosis, it is of interest that the gene expression signature in RAS is similar to rejection post kidney transplantation which could demonstrate that similar mechanisms are in place. A study including more tissue or a prospective study are further needed to validate these findings.
- Copyright ©the authors 2017
