Donor-specific antibodies in heart transplantation: can we afford the price or is it too steep to pay?

Abstract

One-third of patients awaiting heart transplant are sensitized and 25-35% of heart allograft recipients develop de novo DSAs. Solid phase assays for DSA measurement have facilitated wider use of antibody monitoring and as such, our experience with DSAs is continuously evolving. DSAs continue to exhibit poor correlation with biopsy-proven rejection. Novel molecular technologies, such as cell-free DNA and the molecular microscope (MMDx, which detects rejection-associated intragraft mRNA transcripts), are emerging as more sensitive methods to capture subclinical graft injury. High-resolution typing techniques are providing insight into the differential immunogenicity of HLA classes through epitope and eplet analysis. As sensitization of the transplant population is continuing to rise, our repertoire of desensitization strategies is also expanding. However, there is an acute need of predictive algorithms to help forecast the responders and the durability of desensitization. Novel immunomodulatory therapies have allowed safely transplanting across a positive crossmatch with good short-term survival but reported greater degree of rejection and lower long-term graft survival. Our experience of outcomes as pertaining to DSAs still originates primarily from single-center studies. Our field is confronted with the challenge to establish common practice algorithms for the monitoring and treatment of DSAs.