Top Molecules Associated with CLAD in Lung Transplants Are Shared Between Mucosal Biopsies, Transbronchial Biopsies, and Kidney Transplant Biopsies at Risk of Progression
1Alberta Transplant Applied Genomics Centre, Edmonton, AB, Canada, 2University of Alberta, Edmonton, AB, Canada, 3., ., AB, Canada
Meeting: 2022 American Transplant Congress
Abstract number: 337
Keywords: Biopsy, Gene expression, Kidney transplantation, Lung transplantation
Topic: Clinical Science » Lung » 64 - Lung: All Topics
Session Information
Session Name: Early and Late Outcomes in Lung Transplantation
Session Type: Rapid Fire Oral Abstract
Date: Monday, June 6, 2022
Session Time: 5:30pm-7:00pm
Presentation Time: 6:10pm-6:20pm
Location: Hynes Room 210
*Purpose: Chronic lung allograft dysfunction (CLAD) is a physiologic state with grave consequences for progression to failure but cannot be diagnosed by biopsy histology. We previously used microarrays to analyze mRNA expression in 635 transbronchial (TBB) and 348 airway mucosal biopsies (3BMB) to identify the top CLAD-selective transcripts in TBB (AJT in press https://doi.org/10.1111/ajt.16895) and 3BMB (ATC2021). There was no overlap in the top 30 CLAD-selective transcripts between TBB and 3BMB. In the present study, we hypothesized that CLAD represents a response to wounding conserved across distressed epithelial tissues and even other organs, including TBBs, 3BMBs, and kidney transplants, and that these would likely be associated with progression.
*Methods: We analyzed 498 TBBs and 324 3BMBs with known CLAD status. All analyses, including volcano plots and gene set enrichment analysis (GSEA) were performed using version 4.1.0 of R.
*Results: Many of the top 30 CLAD-selective transcripts in TBBs were significantly increased in 3BMB with CLAD in Volcano plots (Figure 1A), and vice versa (Figure 1B). GSEA confirmed these associations: 3BMB CLAD genes were significantly associated with CLAD in TBBs and TBB CLAD genes in 3BMBs (both P<0.0001). The top CLAD-selective transcripts in TBBs and 3BMBs generally were not primarily expressed in inflammatory cells but were widely expressed in parenchymal cells of various organs, and also expressed in various cancers. Many of the top TBB and 3BMB transcripts were shared with injured kidneys, correlating strongly with injury principal component 1 (PC1) which is associated with kidney transplant progression to failure (Table 1) (Halloran et al DOI: 10.1111/ajt.16374).
*Conclusions: We conclude that CLAD involves some molecular processes shared across seriously injured tissues in organs that are progressing toward failure. The shared responses in these distressed organs may help to understand the basis of progression and potential opportunities for intervention in all solid organ transplants.
To cite this abstract in AMA style:
Mackova M, Halloran K, Halloran PF. Top Molecules Associated with CLAD in Lung Transplants Are Shared Between Mucosal Biopsies, Transbronchial Biopsies, and Kidney Transplant Biopsies at Risk of Progression [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/top-molecules-associated-with-clad-in-lung-transplants-are-shared-between-mucosal-biopsies-transbronchial-biopsies-and-kidney-transplant-biopsies-at-risk-of-progression/. Accessed May 17, 2025.« Back to 2022 American Transplant Congress