Molecular assessment of rejection and injury in lung transplant biopsies
Autor: | Gregory I Snell, I. Timofte, Walter Klepetko, Stephen C. Juvet, Glen P. Westall, Michael D. Parkes, Antoine Roux, Peter Jaksch, Philip F. Halloran, Kieran Halloran, Ramsey R. Hachem, Elbert P. Trulock, Daniel Kreisel, Shaf Keshavjee, Jessica Chang |
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Rok vydání: | 2019 |
Předmět: |
Graft Rejection
0301 basic medicine Pulmonary and Respiratory Medicine Pathology medicine.medical_specialty Microarray Biopsy Population Disease 030230 surgery 03 medical and health sciences 0302 clinical medicine Archetypal analysis medicine Humans Sampling (medicine) Pathology Molecular education Transplantation education.field_of_study Lung business.industry Histology Kidney Transplantation Sampling variance 030104 developmental biology medicine.anatomical_structure Surgery Cardiology and Cardiovascular Medicine business Lung Transplantation |
Zdroj: | The Journal of Heart and Lung Transplantation. 38:504-513 |
ISSN: | 1053-2498 |
Popis: | 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. |
Databáze: | OpenAIRE |
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