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Gene expression profiling distinguishes a molecular signature for grade 1B mild acute cellular rejection in cardiac allograft recipients
Journal article   Peer reviewed

Gene expression profiling distinguishes a molecular signature for grade 1B mild acute cellular rejection in cardiac allograft recipients

Daniel Bernstein, Gavin E Williams, Howard Eisen, Seema Mital, Jay G Wohlgemuth, Tod M Klingler, Kenneth C Fang, Mario C Deng and Jon Kobashigawa
The Journal of heart and lung transplantation, v 26(12), pp 1270-1280
Dec 2007
DOI: https://doi.org/10.1016/j.healun.2007.09.017
PMID: 18096478
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Adolescent Adult Aged Algorithms Antigens, CD - blood Antigens, CD - genetics Apoptosis Regulatory Proteins - blood Apoptosis Regulatory Proteins - genetics Biopsy Female Gene Expression Profiling GPI-Linked Proteins Graft Rejection - classification Graft Rejection - diagnosis Graft Rejection - genetics Heart Transplantation - adverse effects Humans Male Middle Aged Myocardium - pathology Predictive Value of Tests Prognosis Programmed Cell Death 1 Receptor Semaphorins - blood Semaphorins - genetics Severity of Illness Index Ubiquitin-Protein Ligases - blood Ubiquitin-Protein Ligases - genetics
Gene expression profiling distinguishes the absence or presence of moderate to severe grades of acute cellular rejection in cardiac allograft recipients using a 20-gene classifier. We explored the hypothesis that the rejection classifier also differentiates various forms of mild rejection and we performed sub-analyses based on time post-transplant and confirmatory pathology interpretations. A post hoc analysis of 265 CARGO study patients and 714 clinical encounters focused on the correlation of rejection classifier-derived gene expression (GE) scores for blood samples accompanying endomyocardial biopsies. Biopsy grades assigned by a study center pathologist (center) were re-interpreted by three pathologists (panel) in a blinded manner. Mean GE scores not only differentiated Grades >or=3A from Grade 0 (p < 0.00001, center or panel), but also from Grades 1A or 2 (p < 0.05, center or panel), based on mild rejection sub-groups defined by the ISHLT 1990 grading system. In contrast, mean GE scores for Grades 1B and >or=3A were indistinguishable, using either center or panel interpretation. Sub-group analyses of encounters from 2 to 6 months or >6 months post-transplant showed similar results for the classifier's ability to discriminate moderate to severe rejection from Grades 1A and 2 mild rejection, but indistinguishable mean GE scores for Grades >or=3A and the Grade 1B sub-group. Of the classifier's 11 informative genes, expression of MIR and WDR40 showed statistically significant increases for both Grade 1B and Grade >or=3A rejection, while expression of PDCD1 or SEMA7A showed similar directional patterns without achieving statistical significance. These data demonstrate that GE scores discriminate moderate to severe rejection from Grades 1A and 2 mild rejection. However, a sub-group of mild rejection cases, defined as Grade 1B according to the 1990 grading system, share a molecular signature more consistent with moderate to severe rejection. The clinical relevance of these data remains to be defined.

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Collaboration types
Domestic collaboration
Web of Science research areas
Cardiac & Cardiovascular Systems
Respiratory System
Surgery
Transplantation
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