دورية أكاديمية
أعرض في EDS

Caveats in Interpretation of Molecular Diagnostics in Heart Allografts.

التفاصيل البيبلوغرافية
العنوان: Caveats in Interpretation of Molecular Diagnostics in Heart Allografts.
المؤلفون: Randhawa PS; Department of Pathology, The Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
المصدر: Transplantation [Transplantation] 2024 Jul 01; Vol. 108 (7), pp. 1472-1475. Date of Electronic Publication: 2024 Jan 31.
نوع المنشور: Journal Article; Review
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0132144 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1534-6080 (Electronic) Linking ISSN: 00411337 NLM ISO Abbreviation: Transplantation Subsets: MEDLINE
أسماء مطبوعة: Publication: Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Williams & Wilkins.
مواضيع طبية MeSH: Heart Transplantation*/adverse effects , Graft Rejection*/immunology , Graft Rejection*/diagnosis , Graft Rejection*/genetics , Graft Rejection*/pathology, Humans ; Biopsy ; Molecular Diagnostic Techniques ; Allografts/immunology ; Myocardium/pathology ; Reproducibility of Results ; Pathology, Molecular ; Predictive Value of Tests ; Gene Expression Profiling
مستخلص: Histologic separation of injury, T cell-mediated rejection, or antibody-mediated rejection in allograft heart biopsies is difficult. A critical review of publications was performed to evaluate the caveats of using molecular diagnostics (MDX) to distinguish between these entities. Typically, only 1 to 2 fragments of unknown histologic appearance are evaluated. Archetype and molecular classifier analyses use gene lists derived from histologic labels and associated reproducibility issues influence the accuracy of the derived MDX classes. Archetypes A1, A2, and A3 archetypes created by bioinformatics were renamed no rejection, T cell-mediated rejection, and antibody-mediated rejection despite as little as 40% concordance with histologic diagnoses and overlapping archetype scores. Additional archetypes S4 and minor injury were created using arbitrary cutoffs based on visual examination of principal component analysis plots. Therapeutic implications of the numerous discrepancies with histology remain unexplored. Many MDX-derived observations are ambiguous and open to alternate logical explanations. Better molecular methods and more rigorous validation studies are needed to advance the field. Ideally, these methods should analyze all available biopsy fragments to minimize sampling issues. It is also desirable to incorporate spatial transcriptomics into the workflow, so that gene expression data can be directly compared with the underlying histology lesions.
Competing Interests: The author declares no funding or conflicts of interest.
(Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
References: Stewart S, Winters GL, Fishbein MC, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant. 2005;24:1710–1720.
Berry GJ, Burke MM, Andersen C, et al. The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2013;32:1147–1162.
Loupy A, Duong Van Huyen JP, Hidalgo L, et al. Gene expression profiling for the identification and classification of antibody-mediated heart rejection. Circulation. 2017;135:917–935.
Halloran PF, Madill-Thomsen KS. The molecular microscope diagnostic system: assessment of rejection and injury in heart transplant biopsies. Transplantation. 2023;107:27–44.
Keslar K, Rodriguez ER, Tan CD, et al. Complement gene expression in human cardiac allograft biopsies as a correlate of histologic grade of injury. Transplantation. 2008;86:1319–1321.
Halloran PF, Potena L, Van Huyen JD, et al. Building a tissue-based molecular diagnostic system in heart transplant rejection: the heart molecular microscope diagnostic (MMDx) system. J Heart Lung Transplant. 2017;36:1192–1200.
Madill-Thomsen KS, Reeve J, Aliabadi-Zuckermann A, et al. Assessing the relationship between molecular rejection and parenchymal injury in heart transplant biopsies. Transplantation. 2022;106:2205–2216.
Halloran PF, Madill-Thomsen K, Aliabadi-Zuckermann AZ, et al. Many heart transplant biopsies currently diagnosed as no rejection have mild molecular antibody-mediated rejection-related changes. J Heart Lung Transplant. 2022;41:334–344.
Parkes MD, Aliabadi AZ, Cadeiras M, et al. An integrated molecular diagnostic report for heart transplant biopsies using an ensemble of diagnostic algorithms. J Heart Lung Transplant. 2019;38:636–646.
Halloran PF, Reeve J, Aliabadi AZ, et al. Exploring the cardiac response to injury in heart transplant biopsies. JCI Insight. 2018;3:e123674.
Madill-Thomsen KS, Wiggins RC, Eskandary F, et al. The effect of cortex/medulla proportions on molecular diagnoses in kidney transplant biopsies: rejection and injury can be assessed in medulla. Am J Transplant. 2017;17:2117–2128.
Madill-Thomsen K, Perkowska-Ptasinska A, Bohmig GA, et al.; MMDx-Kidney Study Group. Discrepancy analysis comparing molecular and histology diagnoses in kidney transplant biopsies. Am J Transplant. 2020;20:1341–1350.
Randhawa P, Huang Y, Randhawa P, et al. MMDx® rejection and injury scores in pediatric endomyocardial biopsies: lack of concordance with results of the InterHeart Study. Am J Transplant. 2023;23:WOS:000705310101165.
Randhawa P. The MMDx® diagnostic system: a critical re-appraisal of its knowledge gaps and a call for rigorous validation studies. Clin Transplant. 2022;36:e14747.
Randhawa P. The molecular microscope (MMDX(R)) interpretation of thoracic and abdominal allograft biopsies: putting things in perspective for the clinician. Clin Transplant. 2021;35:e14223.
Randhawa P, Seitz A, Huang Y, et al. The pathology of heart allograft biopsies: discrepancies in interpretation between conventional histology and the molecular microscope diagnostic (MMDx (R)) system. Am J Transplant. 2021;21:361–362A.
Dai H, Lan P, Zhao D, et al. PIRs mediate innate myeloid cell memory to nonself MHC molecules. Science. 2020;368:1122–1127.
Zhao D, Abou-Daya KI, Dai H, et al. Innate allorecognition and memory in transplantation. Front Immunol. 2020;11:918.
Randhawa P, Roufosse C. The expanding spectrum of antibody-mediated rejection: should we include cases where no anti-HLA donor-specific antibody is detected? Am J Transplant. 2019;19:622–624.
Sentis A, Kers J, Yapici U, et al. The prognostic significance of glomerular infiltrating leukocytes during acute renal allograft rejection. Transpl Immunol. 2015;33:168–175.
Chikeka IO, Paulk A, Haririan A, et al. Concurrent cytomegalovirus glomerulitis and BK polyomavirus-associated nephropathy in a kidney allograft biopsy. Transpl Infect Dis. 2016;18:247–250.
Callemeyn J, Senev A, Coemans M, et al. Missing self-induced microvascular rejection of kidney allografts: a population-based study. J Am Soc Nephrol. 2021;32:2070–2082.
Randhawa P, Huang Y, Randhawa P, et al. Correlating histology, immunohistochemical, & serologic data in heart transplant recipients: implications for molecular diagnostic assays. Am J Transplant. 2022;22:838.
تواريخ الأحداث: Date Created: 20240131 Date Completed: 20240625 Latest Revision: 20240625
رمز التحديث: 20240626
DOI: 10.1097/TP.0000000000004895
PMID: 38294835
قاعدة البيانات: MEDLINE
الوصف
تدمد:1534-6080
DOI:10.1097/TP.0000000000004895