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Many heart transplant biopsies currently diagnosed as no rejection have mild molecular antibody-mediated rejection-related changes

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العنوان: Many heart transplant biopsies currently diagnosed as no rejection have mild molecular antibody-mediated rejection-related changes
المؤلفون: Daniel Kim, Katelynn S. Madill-Thomsen, Martin Cadeiras, Andreas Zuckermann, Jon A. Kobashigawa, Peter S. Macdonald, Luciano Potena, Philip F. Halloran, Eugene C. DePasquale, Johannes Gökler, Josef Stehlik, Marisa G. Crespo-Leiro, Mario C. Deng, A. Aliabadi-Zuckermann, Keyur B. Shah
المصدر: RUC. Repositorio da Universidade da Coruña
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بيانات النشر: Elsevier BV, 2022.
سنة النشر: 2022
مصطلحات موضوعية: Graft Rejection, Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Microarray, Biopsy, Inflammation, Rejection, Antibodies, Archetypal analysis, medicine, Humans, Prospective Studies, 1102 Cardiorespiratory Medicine and Haematology, Microscopy, Transplantation, Ejection fraction, biology, medicine.diagnostic_test, business.industry, Myocardium, Heart, Cross-Sectional Studies, Molecular Diagnostic Techniques, Antibody mediated rejection, biology.protein, Heart Transplantation, Surgery, Gene expression, medicine.symptom, Antibody, Cardiology and Cardiovascular Medicine, business
الوصف: BackgroundThe Molecular Microscope (MMDx) system classifies heart transplant endomyocardial biopsies as No-rejection (NR), Early-injury, T cell-mediated (TCMR), antibody-mediated (ABMR), mixed, and possible rejection (possible TCMR, possible ABMR). Rejection-like gene expression patterns in NR biopsies have not been described. We extended the MMDx methodology, using a larger data set, to define a new "Minor" category characterized by low-level inflammation in non-rejecting biopsies.MethodsUsing MMDx criteria from a previous study, molecular rejection was assessed in 1,320 biopsies (645 patients) using microarray expression of rejection-associated transcripts (RATs). Of these biopsies, 819 were NR. A new archetypal analysis model in the 1,320 data set split the NRs into NR-Normal (N = 462) and NR-Minor (N = 359).ResultsCompared to NR-Normal, NR-Minor were more often histologic TCMR1R, with a higher prevalence of donor-specific antibody (DSA). DSA positivity increased in a gradient: NR-Normal 24%; NR-Minor 34%; possible ABMR 42%; ABMR 66%. The top 20 transcripts distinguishing NR-Minor from NR-Normal were all ABMR-related and/or IFNG-inducible, and also exhibited a gradient of increasing expression from NR-Normal through ABMR. In random forest analysis, TCMR and Early-injury were associated with reduced LVEF and increased graft loss, but NR-Minor and ABMR scores were not. Surprisingly, hearts with MMDx ABMR showed comparatively little graft loss.ConclusionsMany heart transplants currently diagnosed as NR by histologic or molecular assessment have minor increases in ABMR-related and IFNG-inducible transcripts, associated with DSA positivity and mild histologic inflammation. These results suggest that low-level ABMR-related molecular stress may be operating in many more hearts than previously estimated. (ClinicalTrials.gov #NCT02670408).
وصف الملف: Print-Electronic; application/pdf
تدمد: 1053-2498
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::059aad28b62c751a2cdcec3a8707d82c
https://doi.org/10.1016/j.healun.2021.08.004
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....059aad28b62c751a2cdcec3a8707d82c
قاعدة البيانات: OpenAIRE
الوصف
تدمد:10532498