Antibody-mediated rejection probably causes the majority of acute graft losses. More than 40% of the patients with antibody-mediated rejection have allograft dysfunction. Although its existence as a self defined entity was controversial over the last decade, it is increasingly accepted in heart transplantation, likely attributable to improved methods of detection but also, it is believed that changing trends in clinical practice including selection of patients for transplantation on mechanical circulatory support and the development of more effective combinations of immunosuppressive drugs against acute cellular rejection may also contribute to an increased probability of antibody-mediated rejection.

The pathological findings in the transplanted heart of patients experiencing antibody-mediated rejection include interstitial edema, prominent endothelial cells, and occasional inflammatory cells. The diagnosis of antibody-mediated rejection is supported by detection of antibodies with specificity for donor-antigens and products of Complement activation promoting injury of donor endothelial cells and the underlying tissues. This process can be very well delineated by immunofluorescence which is currently the histological technique used to definitively diagnose antibody-mediated rejection by highlighting immunoglobulin M and G, complement C3 fraction and C1q within the endothelial cells. Most recently it has been shown that staining for the complement split product C4d in tissues is more sensitive than histological features and correlated well with the presence of antidonor alloantibodies but it can be also found related to ischemia-reperfusion injury, cardiac allograft vasculopathy (chronic rejection) infection and heterologous antiserum therapy.

In our lab, Manuel Prinz Von Bayern in collaboration with Dr. Charles Marboe, within the context of the CARGO study is working on elucidating the links between acute cellular rejection, chronic rejection and antibody mediated rejection by correlating C4d staining with functional genomics information collected in the CARGO study.