Molecular Assessment of Microcirculation Injury in Formalin-Fixed Human Cardiac Allograft Biopsies With Antibody-Mediated Rejection

• DOI: 10.1111/ajt.13956
• Publication Date: 2016-07-12T07:17:38Z
• Authors: B. Afzali; E. Chapman; M. Racapé; B. Adam; P. Bruneval; F. Gil; D. Kim; L. Hidalgo; P. Campbell; B. Sis; J.P. Duong Van Huyen; M. Mengel
• Keywords: Adult; Graft Rejection; Male; Biopsy; Medizin; 03 medical and health sciences; 0302 clinical medicine; Isoantibodies; Formaldehyde; Humans; Retrospective Studies; Heart Failure; Gene Expression Profiling; Microcirculation; Graft Survival; Middle Aged; Allografts; Prognosis; 3. Good health; Killer Cells, Natural; Heart Transplantation; Female; Biomarkers; Follow-Up Studies

Precise diagnosis of antibody-mediated rejection (AMR) in cardiac allograft endomyocardial biopsies (EMBs) remains challenging. This study assessed molecular diagnostics human EMBs with AMR. A set 34 endothelial, natural killer cell and inflammatory genes was quantified 106 formalin-fixed, paraffin-embedded classified according to 2013 International Society for Heart Lung Transplantation (ISHLT) criteria. The gene expression compared between ISHLT diagnoses correlated donor-specific antibody (DSA), endothelial injury by electron microscopy (EM) prognosis. Findings were validated an independent 57 EMBs. In the training (n = 106), AMR cases 70) showed higher than acute cellular (ACR; n 21, p < 0.001) controls 15, 0.0001). Anti-HLA DSA positivity associated (p 0.01). Endothelial strongly expression, specifically (r 0.62, 0.002). Receiver operating characteristic curve analysis diagnosing greater accuracy (area under [AUC] 79.88) (AUC 70.47) C4d 70.71). patients 17) sequential biopsies, increasing inferior prognosis 0.034). These findings confirmed validation set. conclusion, biopsy-based assessment microcirculation has potential improve transplants.