The Search for a Gold Standard to Detect Rejection in Heart Transplant Patients
Are We There Yet?
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Article, see p 917
Heart transplantation remains the only definitive treatment for end-stage heart failure. Advances in immunosuppressive therapies have improved outcomes; however, allograft rejection is still a major impediment to survival. Although cellular rejection rates have been declining, rates of antibody-mediated rejection (AMR) have shown little improvement and afflict 10% to 20% of patients.1 AMR correlates with adverse outcomes, including hemodynamic compromise rejection, cardiac allograft vasculopathy, and death.1 Despite efforts from the International Society of Heart and Lung Transplantation (ISHLT) to standardize the diagnosis and grading of AMR,2 subjectivity in interpreting histological findings will continue to be an insurmountable obstacle. This is not helped by a limited understanding of the pathophysiology of the disease.2
In this issue of Circulation, Loupy et al3 address this knowledge gap by using gene expression profiling in endomyocardial biopsy (EMB) samples from heart transplant recipients with AMR. Gene expression profiling of allograft biopsy samples using RNA extraction and microarray analysis was performed on 71 biopsy samples from 55 patients who were diagnosed with AMR using conventional histology. They were compared with a matched control group of 55 rejection-free and acute cellular rejection (ACR) patients to eliminate any overlap in gene expression between the 2 types of rejection. AMR was diagnosed by using the 2013 ISHLT pathological grading system (Table), and patients with all grades were included. This study is the first to characterize the molecular landscape of AMR in heart transplantation by using EMB samples. The results showed that 4 gene sets are expressed in AMR and include …