Caveats in Interpretation of Molecular Diagnostics in Heart Allografts

口译(哲学) 医学 心脏移植 重症监护医学 心脏病学 计算机科学 心力衰竭 程序设计语言
作者
Parmjeet Randhawa
出处
期刊:Transplantation [Ovid Technologies (Wolters Kluwer)]
标识
DOI:10.1097/tp.0000000000004895
摘要

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.
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