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    Molecular assessment of rejection and injury in lung transplant biopsies

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    Author
    Halloran, K.M.
    Parkes, M.D.
    Chang, J.
    Date
    2019
    Journal
    Journal of Heart and Lung Transplantation
    Publisher
    Elsevier USA
    Type
    Article
    
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    https://doi.org/10.1016/j.healun.2019.01.1317
    Abstract
    BACKGROUND: Improved understanding of lung transplant disease states is essential because failure rates are high, often due to chronic lung allograft dysfunction. However, histologic assessment of lung transplant transbronchial biopsies (TBBs) is difficult and often uninterpretable even with 10 pieces. METHODS: We prospectively studied whether microarray assessment of single TBB pieces could identify disease states and reduce the amount of tissue required for diagnosis. By following strategies successful for heart transplants, we used expression of rejection-associated transcripts (annotated in kidney transplant biopsies) in unsupervised machine learning to identify disease states. RESULTS: All 242 single-piece TBBs produced reliable transcript measurements. Paired TBB pieces available from 12 patients showed significant similarity but also showed some sampling variance. Alveolar content, as estimated by surfactant transcript expression, was a source of sampling variance. To offset sampling variation, for analysis, we selected 152 single-piece TBBs with high surfactant transcripts. Unsupervised archetypal analysis identified 4 idealized phenotypes (archetypes) and scored biopsies for their similarity to each: normal; T-cell?mediated rejection (TCMR; T-cell transcripts); antibody-mediated rejection (ABMR)-like (endothelial transcripts); and injury (macrophage transcripts). Molecular TCMR correlated with histologic TCMR. The relationship of molecular scores to histologic ABMR could not be assessed because of the paucity of ABMR in this population. CONCLUSIONS: Molecular assessment of single-piece TBBs can be used to classify lung transplant biopsies and correlated with rejection histology. Two or 3 pieces for each TBB will probably be needed to offset sampling variance.
    Keyword
    antibody-mediated rejection
    gene expression
    microarray
    surfactant
    T-cell?mediated rejection
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85061540376&doi=10.1016%2fj.healun.2019.01.1317&partnerID=40&md5=efe44e91218030acd4bfe55ae92c1ff0; http://hdl.handle.net/10713/10691
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.healun.2019.01.1317
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