Date: Sunday, June 12, 2016
Session Time: 4:30pm-6:00pm
Presentation Time: 4:42pm-4:54pm
Location: Room 313
Purpose: The main diagnostic platform for rejection in lung transplant recipients is histology of transbronchial biopsies (TBB), a test with a poor performance and safety profile. Microarray analysis of kidney transplant biopsies has been shown to produce rapid, accurate detection of rejection in small pieces of tissue. We used microarray analysis of transbronchial and mucosal biopsies (MB) in an attempt to detect the molecular changes of T-cell mediated inflammation (TCMI).
Methods: We analyzed 29 TBB and 27 MB from 26 lung transplant recipients, between 1-184 months post-transplant undergoing indication biopsies. We obtained 5-10 TBB and 3 MB per patient (1 bite for microarray analysis, remainder for histology). We assessed specimens for molecular changes proven to be associated with TCMI (pathogenesis based transcript sets or PBTs), based on prior work in kidney and heart transplants, and compared this expression to sets of genes expressed in normal lung tissue (LT1,LT2) via Spearman correlation.
Results: High quality RNA was assessable in 100% of samples, even when histology was not. PBTs were detectible in TBB and MB specimens. PBTs correlated negatively with LTs in almost all cases. Expression of transcripts associated with interferon-gamma (IFNG), effector T-cells, and injury all correlated with loss of LT1, indicating parenchymal de-differentiation. The same relationship could be demonstrated in both TBB and MB (Table 1).
Conclusion: Single TBB and MB specimens can be read for molecular changes of TCMI, and correlate with loss of lung transcripts indicating functional deterioration. This confirms that the molecular diagnostic methods emerging in kidney and heart transplantation are practical for both TBB and MB, and will hopefully allow us to standardize microarray analysis as a diagnostic platform for lung transplants. This has the potential to quantify rejection and injury, while doing so in a safer biopsy type, with the ultimate goal of guiding improvements in patient care.
CITATION INFORMATION: Halloran K, Chang J, Ramassar V, Weinkauf J, Kapasi A, Lien D, Reeve J, Halloran P. Microarray Analysis of Transbronchial and Mucosal Biopsies in Lung Transplant Recipients Detects Molecular Changes of T-Cell Mediated Inflammation. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Halloran K, Chang J, Ramassar V, Weinkauf J, Kapasi A, Lien D, Reeve J, Halloran P. Microarray Analysis of Transbronchial and Mucosal Biopsies in Lung Transplant Recipients Detects Molecular Changes of T-Cell Mediated Inflammation. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/microarray-analysis-of-transbronchial-and-mucosal-biopsies-in-lung-transplant-recipients-detects-molecular-changes-of-t-cell-mediated-inflammation/. Accessed April 7, 2020.
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