Pathologic basis of antibody-mediated organ transplant rejection: from pathogenesis to diagnosis

Although antibody-mediated rejection of clinical organ transplants has been recognized more than a half-century ago, our understanding of its pathological/clinical phenotypes has dramatically increased over the past decade. This review highlights the pathological/clinical spectrum of ABMR and discusses its microscopic pathology in relationship with pathogenesis.

Newly recognized pathological manifestations of ABMR are: (1) C4d-negative active ABMR, which cannot be definitely diagnosed by current diagnostic systems and often remains underdetected. Novel molecular diagnostic tests can fill this diagnostic gap but these new tests are yet to be prepared for routine application; (2) antibody-mediated vascular rejection, which is misclassified by the current Banff Classification, is therefore inadequately treated and has a high risk for transplant failure; and (3) subclinical (insidious) microvascular inflammation, which can be with or without complement activation, predicts progression to chronic rejection, transplant dysfunction, and failure.

A major progress has been made in understanding of ABMR of clinical transplants in the last 5 years. New pathology types of ABMR are not appropriately classified and updates to the Banff diagnostic criteria are required. Better diagnosis would help develop effective antiantibody treatment strategies and improve long-term outcomes for patients.