Background: The Molecular Microscope Diagnostic System (MMDx) may overcome histology shortcomings. Previous studies have simply examined discrepant findings but have not attempted to determine clinical endpoints. To measure performance, clinical outcomes are strongly required.
Methods: This single-center cohort study described discrepancies between MMDx and histology from 51 kidney transplant recipients (KTRs) and analyzed 72 indication biopsies, including 21 follow-up biopsies. Clinical performance was assessed by a combined endpoint of graft failure, rejection on follow-up biopsy, de novo donor-specific antibody, and improvement of kidney allograft function upon antirejection treatment.
Results: MMDx agreed in 33 (65%) and differed in 18 (35%) of 51 KTRs. Most discrepancies occurred in biopsies called no rejection by MMDx and rejection by histology (15/24, 63%). In contrast, in biopsies called rejection by MMDx, 3 were classified as no rejection by histology (3/27, 11%). Discrepant findings between MMDx and histology occurred following delayed graft function and MMDx from biopsies with a low percentage of cortex. Among 15 biopsies classified as no rejection by MMDx but rejection by histology, the clinical course suggested no rejection in 9 cases. Six KTRs reached the endpoint, showing predominant t ≥ 2 lesions.
Conclusions: The most often occurring discrepancy is rejection by histology but no rejection by MMDx. As more KTRs do not meet the combined endpoint for rejection, MMDx might be clinically useful in these discrepant cases. Although strong histological findings have priority in indicating the treatment, clinical implementation of MMDx could strengthen treatment strategies.
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http://dx.doi.org/10.1097/TP.0000000000004284 | DOI Listing |
Transplant Direct
January 2025
Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Background: Presensitized patients with circulating donor-specific antibodies (DSAs) before transplantation are at risk for antibody-mediated rejection (AMR). Peritransplant desensitization mitigates but does not eliminate the alloimmune response. We examined the possibility that subthreshold AMR activity undetected by histology could be operating in some early biopsies.
View Article and Find Full Text PDFObjectives: To evaluate the clinical implications of adjunctive molecular gene expression analysis (MMDx ) of biopsy specimens in heart transplant (HT ) recipients with suspected rejection.
Introduction: Histopathological evaluation remains the standard method for rejection diagnosis in HT. However, the wide interobserver variability combined with a relatively common incidence of "biopsy-negative" rejection has raised concerns about the likelihood of false-negative results.
Nephrol Dial Transplant
June 2024
University Hospital Zurich, Department of Nephrology; Zurich, Switzerland.
Background And Hypothesis: Isolated Tubulitis, Borderline Changes, and Isolated Arteritis suspicious for histologic T cell-mediated rejection (hTCMR) remain findings of uncertain significance. Although the Molecular Microscope Diagnostics System (MMDx) has not been trained on those lesions, it was suggested that MMDx might reclassify a subgroup to molecular TCMR (mTCMR).
Methods: In this single-center cohort of 326 consecutive, unselected kidney allograft biopsies assessed by histology and MMDx, we analyzed 249 cases with Isolated Tubulitis (i0, t1-3, v0; n=101), Borderline Changes (according to Banff 2022, v0; n=9), Isolated Arteritis (no borderline, v1; n=37), No Inflammation (i0, t0, v0; n=67) and a Positive Control Cohort (hTCMR, n=27; Mixed histologic Rejection, n=8; both according to Banff 2022; total n=35).
Transpl Immunol
August 2024
Department of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Until now, the ability to predict or retard immune-mediated rejection events after lung transplantation is still limited due to the lack of specific biomarkers. The pressing need remains to early diagnose or predict the onset of chronic lung allograft dysfunction (CLAD) and its differential phenotypes that is the leading cause of death. Omics technologies (mainly genomics, epigenomics, and transcriptomics) combined with advanced bioinformatic platforms are clarifying the key immune-related molecular routes that trigger early and late events of lung allograft rejection supporting the biomarker discovery.
View Article and Find Full Text PDFClin Sci (Lond)
June 2024
Department of Medicine, University of Alberta, Edmonton, AB, Canada.
There is a major unmet need for improved accuracy and precision in the assessment of transplant rejection and tissue injury. Diagnoses relying on histologic and visual assessments demonstrate significant variation between expert observers (as represented by low kappa values) and have limited ability to assess many biological processes that produce little histologic changes, for example, acute injury. Consensus rules and guidelines for histologic diagnosis are useful but may have errors.
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