The Molecular Microscope (MMDX^R) interpretation of thoracic and abdominal allograft biopsies: Putting things in perspective for the clinician

Abstract

There is no question that molecular analyses are complementary to and can enhance biopsy interpretation, as has been outlined in a comprehensive review. 3 Specifically, MMDx can reveal tissue changes not visible by light microscopy, enhance the diagnosis of antibody-mediated rejection, provide superior methods for assessing tubular injury, develop prognostic classifiers using thousands of genes, and potentially provide means to objectively quantify tissue inflammation (Table 1). The purpose of the present commentary is to provide balance to the literature by offering a more detailed account of its caveats and limitations, while at the same time acknowledging its ability to enhance patient care. Several key concepts inherent to transplantation diagnostics need to be explained to put this subject in perspective. | Diagnosis versus grading of diseaseConventional histology has played a major role in the development of solid organ transplantation and has contributed to the excellent outcomes that are now routinely achieved. Histology is often referred

Utility of Banff Human Organ Transplant Gene Panel in Human Kidney Transplant Biopsies

“…48 What accounts for this disparity and whether it is useful are questions under discussion. 61,62 Are transcripts more accurate than Banff diagnostic criteria or the reverse? Pathologic criteria may underestimate CAMR, activity, tubular injury, and the extent of inflammation, show some nonspecificity [63][64][65] and are not well correlated with mRNA expression.…”

The MMDx®diagnostic system: A critical re‐appraisal of its knowledge gaps and a call for rigorous validation studies

“…An opinion piece published in this journal last year highlighted the limitations of this promising technology. 1 McCloskey et al have now responded to this article expressing disagreement with several of the points made in that article. 2 I welcome this opportunity to respond to the issues raised, and re-emphasize the substantial validation studies that are needed before MMDx can be regarded as standard of care.…”

“…As is true for other currently available molecular tests, practicing physicians seeking to understand MMDX capabilities need to be able to make a distinction between commercial hype and rigorous science. An opinion piece published in this journal last year highlighted the limitations of this promising technology 1 . McCloskey et al.…”

Diagnosis of T-cell-mediated kidney rejection by biopsy-based proteomic biomarkers and machine learning

“…As the base of commercially available diagnostic tests, mRNA profiling is available as a test that is marketed as the Molecular Microscope or MMDx ® system. It offers prospects of improved disease classification but has several inherent limitations such as high cost of mRNA extraction ( 7 , 8 ). In addition, it’s easy to miss the core with real disease information since the developed technologies become dependent analysis of a small tissue fragment taken from a longer core sent for routine histology ( 9 , 10 ).…”