Impact of rejection-related immune responses on the initiation and progression of cardiac allograft vasculopathy

Given the causal association between acute rejection (AR) and CAV, early detection of AR, selection of appropriate rejection management strategies and close monitoring of AR therapy results, can delay the development and/or aggravation of CAV. Due to the complexity of AR surveillance, no single invasive or noninvasive diagnostic method can provide all the needed information for preventing AR-related coronary vascular damages. Certain combinations of available non-invasive surveillance techniques can detect patients at imminent risk for AR and therefore enable the replacement of unnecessary routine surveillance endomyocardial biopsies (EMBs) by a lower number of diagnostic EMBs and also help for severity grading of biopsy-proven AR. Decisions about the need for AR therapy, selection of therapies, and determination of therapy duration can also help to delay the development and progression of CAV. Regarding this, the search for antibody-mediated rejection in all EMBs is mandatory and the use of certain non-invasive surveillance methods like sensitive echocardiographic techniques, monitoring of complement-activating donor specific antibodies and gene expression analysis can be particularly useful. Given its ability to identify patients at high risk for future rejections, gene expression analysis also facilitates an individualized immunosuppression. This article gives an overview of the current knowledge about the immunology of CAV and its linkage with AR. Special attention is focused on the impact of asymptomatic early and late low-grade ARs on the pathogenesis and the course of CAV. Overall, the review aimed to provide a theoretical and practical basis for all those engaged in this particularly demanding upto-date topic.