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Gene expression markers to segregate lung transplant rejection phenotypes

Stijn Verleden, Joshua Yang, Tara Sigdel, Juliane liberto, Geert Verleden, Robin Vos, bart Vanaudenaerde, Minnie Sarwal
European Respiratory Journal 2017 50: OA1992; DOI: 10.1183/1393003.congress-2017.OA1992
Stijn Verleden
1KU Leuven, Leuven, Belgium
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Joshua Yang
2UCSF, San Francisco, United States of America
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Tara Sigdel
2UCSF, San Francisco, United States of America
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Juliane liberto
2UCSF, San Francisco, United States of America
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Geert Verleden
1KU Leuven, Leuven, Belgium
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Robin Vos
1KU Leuven, Leuven, Belgium
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bart Vanaudenaerde
1KU Leuven, Leuven, Belgium
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Minnie Sarwal
2UCSF, San Francisco, United States of America
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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.

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Gene expression markers to segregate lung transplant rejection phenotypes
Stijn Verleden, Joshua Yang, Tara Sigdel, Juliane liberto, Geert Verleden, Robin Vos, bart Vanaudenaerde, Minnie Sarwal
European Respiratory Journal Sep 2017, 50 (suppl 61) OA1992; DOI: 10.1183/1393003.congress-2017.OA1992

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Gene expression markers to segregate lung transplant rejection phenotypes
Stijn Verleden, Joshua Yang, Tara Sigdel, Juliane liberto, Geert Verleden, Robin Vos, bart Vanaudenaerde, Minnie Sarwal
European Respiratory Journal Sep 2017, 50 (suppl 61) OA1992; DOI: 10.1183/1393003.congress-2017.OA1992
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