This issue reports a case where the authors can be congratulated on having saved the life of a patient who originally suffered from giant cell myocarditis and had been treated with cyclosporine (CyA), azathioprine (AZA) and corticosteroids (PDN) for 4 years before clinically deteriorating and been subjected to heart transplantation (HTx) [1]. The pretransplant work-up included human leukocyte antigen (HLA)-typing of both patient and donor, screening for anti-HLA antibodies and cross-match with regard to T- and B-cells being negative. Postoperatively, conventional immunosuppression (CyA, AZA and PDN) was introduced. There were three HLA Class I and one HLA Class II allele mismatches between donor and recipient. The first endomyocardial biopsy (EMB) showed mild rejection (ISHLT 1R) without C4d deposition in immunohistochemistry. The second EMB (3 weeks postoperatively) revealed severe macrophage (CD68+), and eosinophilic and lymphocytic infiltration, again without C4d deposition. The patient developed fever without clinical signs of infection and was treated under the presumption of acute cellular rejection (ACR). After initial stabilization, the patient developed cardiogenic shock 2 days later, which required urgent treatment with extracorporeal membrane oxygenation, followed by the implantation of a biventricular assist device the next day. At that time, EMB showed severe ACR (ISHLT 3R) and antibodymediated rejection (AMR), strongly positive for C4d [2, 3]. The cytotoxic T- and B-cell cross-match tests remained negative. The endothelial precursor cells cross-match test (EPC-XM; XM-ONE ® , AbSorber AB, Sweden) was synchronously performed with EMBs, measuring serum levels of the amount of antiendothelial-cell antibodies (AECAs), either against donorspecific EPC’s or against autoreactive EPC’s (the patient’ so wn EPCs). After initially being negative, donor-specific AECA became positive at the first EMB (ISHLT 1R), but autoreactive AECAs were still negative. At the time of acute graft failure, the test was surprisingly positive for both donor-specific and autoreactive IgM antiendothelial AECA, but not for donor IgG AECA. The authors conclude that severe AMR was caused by non-HLA, AECAs. Epicrisis was successfully treated by plasmapheresis, intravenous immunoglobulin (IVIgG), rituximab, muronomab-CD3, bortezomib and re-HTx. One month after re-HTx, the patient had ACR (ISHLT 2R), but remained free of AMR. During the last 15 years, AMR became a topic of major clinical relevance. Potential explanations are improved diagnostic tests and the rising population of patients having undergone VAD implantation before HTx. Its pathophysiology remains unknown to date. AMR is often associated with haemodynamic compromise, increased mortality and development of graft coronary artery disease (CAD). Younger age, congenital heart disease, positive donor-specific cross-match, positive panel reactive antibody (PRA) titres, sensitization to OKT3, CMV seropositivity, previous blood transfusions and female gender have been identified as risk factors for AMR [4].