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Purpose of Review <p>Heart and lung transplantation both face challenges in the diagnosis of acute rejection, which mainly relies on histology with poor interobserver agreement and limited performance characteristics. This limits clinicians’ ability to assess acute rejection, which can be a substantial contributor to graft failure and death. One of the pathways to improve this is through novel molecular diagnostic methods. These methods hold potential to provide mechanistic insights into rejection pathways, reduce rejection assessment variability, reduce biopsy requirements, and improve patient outcomes. This review details the recent advances in this area and discusses their potential role in the future.</p> Recent Findings <p>The most important advances in lung transplantation have been the evolving role of donor-derived cell free DNA (dd-cfDNA) and its ability to detect injured lung tissue, including rejection; the role of lung tissue transcriptomics to characterize rejection in multiple specimen types (transbronchial, endobronchial, and bronchial brush); and exhaled volatile compounds to detect rejection. In heart transplantation, dd-cfDNA and tissue transcriptomics have encouragingly evolved from experimental platforms to clinical use, with some centers shifting their clinical practise. Meanwhile, non-invasive gene expression profiling of peripheral blood has been shown to reduce surveillance biopsies without affecting safety, while other tests like circulating microRNA and extracellular vesicles continue their development. In some heart transplant programs, this is now being used to reduce biopsy frequency, fundamentally changing clinician practice and the patient experience.</p> Summary <p>Thoracic transplantation is changing, with new molecular tests that promise new dimensions of information for clinicians and patients. The future of clinical practice in these areas will likely involve multimodal assessment of conventional clinical tools and next generation molecular tests, in the hopes of helping patients live longer, better lives.</p>

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Molecular Phenotyping of Acute Rejection in Thoracic Transplantation

  • 期刊论文

  • 发表日期：

    2026年6月17日

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  • Kieran Halloran,
  • Philip Halloran

摘要

Purpose of Review

Heart and lung transplantation both face challenges in the diagnosis of acute rejection, which mainly relies on histology with poor interobserver agreement and limited performance characteristics. This limits clinicians’ ability to assess acute rejection, which can be a substantial contributor to graft failure and death. One of the pathways to improve this is through novel molecular diagnostic methods. These methods hold potential to provide mechanistic insights into rejection pathways, reduce rejection assessment variability, reduce biopsy requirements, and improve patient outcomes. This review details the recent advances in this area and discusses their potential role in the future.

Recent Findings

The most important advances in lung transplantation have been the evolving role of donor-derived cell free DNA (dd-cfDNA) and its ability to detect injured lung tissue, including rejection; the role of lung tissue transcriptomics to characterize rejection in multiple specimen types (transbronchial, endobronchial, and bronchial brush); and exhaled volatile compounds to detect rejection. In heart transplantation, dd-cfDNA and tissue transcriptomics have encouragingly evolved from experimental platforms to clinical use, with some centers shifting their clinical practise. Meanwhile, non-invasive gene expression profiling of peripheral blood has been shown to reduce surveillance biopsies without affecting safety, while other tests like circulating microRNA and extracellular vesicles continue their development. In some heart transplant programs, this is now being used to reduce biopsy frequency, fundamentally changing clinician practice and the patient experience.

Summary

Thoracic transplantation is changing, with new molecular tests that promise new dimensions of information for clinicians and patients. The future of clinical practice in these areas will likely involve multimodal assessment of conventional clinical tools and next generation molecular tests, in the hopes of helping patients live longer, better lives.