The Multifaceted Role of Non-human Leukocyte Antigens' Immune Response in Renal Allograft Rejection

In renal transplantation (RT), human leukocyte antigens (HLA) expressed on donor cells are the principal targets of the recipient's immune system. In addition to classical HLA-alloantibodies, the importance of non-HLA antibodies (Abs) in RT is being increasingly recognized. The majority of non-HLA Abs are considered as autoantibodies as they are directed against cryptic autoantigens of vascular endothelium, which express following tissue (graft) injury. The mechanisms by which these Abs are produced and induce rejection are not fully understood. This review discusses the spectrum of non-HLA Abs, their putative pathogenetic mechanisms, clinical relevance, and their relationship with graft survival and rejection in RT.