The Importance of Non-HLA Antibodies After Heart Transplant

Abstract

Antibodies to human leukocyte antigens (HLA) are associated with adverse patient and allograft outcomes after heart transplantation. Non-HLA antibodies have increasingly been recognized as important mediators of rejection, cardiac allograft vasculopathy (CAV), and allograft injury. In particular, these antibodies have been implicated in a subset of heart transplant recipients who have clinical and/or pathologic evidence of antibody-mediated rejection in the absence of detectable antibodies against HLA. Non-HLA antigens have been identified to have important roles in both the innate and adaptive immune response in transplantation. These antigens are predominantly expressed on vascular endothelium of the donor heart and include major histocompatibility class I related chain A (MICA), G protein coupled receptor angiotensin II type 1 receptor (AT1R), cytoskeletal elements such as myosin and vimentin. A growing number of studies have demonstrated antibodies to these antigens in rejection and development of CAV. At present, non-HLA antibodies are not routinely monitored post-transplant, and laboratory evaluation remains non-standardized. Further investigation is required to improve the detection of non-HLA antibodies, define pathophysiological mechanisms involved in allograft injury, and better understand their impact on clinical outcomes. Non-HLA antibodies have been identified as important mediators of rejection, allograft dysfunction, and CAV in heart transplantation. Ongoing investigations and improving laboratory detection methods will determine their potential role in post-transplant risk stratification and management.