Sensitization to endothelial cell antigens: Unraveling the cause or effect paradox

Abstract Anti-endothelial cell antibodies (AECAs) have been correlated with increased acute and chronic rejection across all organ types and early graft dysfunction in kidney and heart transplantation. Nevertheless, the lack of appropriate tools and clear criteria for defining injurious versus non-injurious AECAs prohibits their routine inclusion in clinical risk assessments and diagnostic algorithms for antibody mediated injury. Clinical characterization of AECAs is complicated due to the wide range of polymorphic and non-polymorphic antigens expressed across different vascular tissues and the diverse array of specificities observed between individuals. This complexity is also reflected in the broad spectrum of reported injury phenotypes. AECAs detected at time of allograft dysfunction may represent biomarkers of past vascular injury or active contributors to a current rejection process. New tools within the fields of proteomics, genomics, bioinformatics, and imaging are currently being validated and hold great promise for unraveling the AECA paradox.