Human leukocyte antigen antibodies in chronic transplant vasculopathy—mechanisms and pathways

Transplant recipients exhibiting posttransplant antibodies are at a higher risk for acute and chronic antibody mediated rejection (AMR). The primary alloantigens recognized by antibodies in recipients with AMR are the highly polymorphic HLA class I and class II molecules expressed on the surface of the endothelial cells (ECs) of the graft. Traditionally, anti-HLA antibodies were thought to mediate graft injury through complement-dependent mechanisms. However, recent studies indicate that antibodies can also contribute to alterations in EC function through complement-independent mechanisms by transducing intracellular signals. Anti-HLA antibodies transduce signals that are both pro-inflammatory and pro-proliferative suggesting mechanistic roles in acute and chronic AMR.