Purpose Of Review: Although chronic rejection is currently one of the main causes of long-term allograft failure, its pathogenesis remains elusive, thereby preventing the development of effective therapy.
Recent Findings: Recent advances in the comprehension of the pathophysiology of chronic inflammatory diseases could shed new light on the pathogenesis of chronic rejection. Lymphoid neogenesis is a mechanism responsible for the progressive organization of chronic inflammatory infiltrates into functional ectopic germinal centers, which has been recently evidenced in various pathological situations sharing a common feature: the failure of the immune response to eradicate the targeted antigens. Chronic rejection is such a situation as it results from a sustained alloimmune response against the donor's antigens that are constantly replenished by the grafted tissue. Accordingly, functional ectopic germinal centers develop within chronically rejected organs.
Summary: During chronic rejection, the graft is simultaneously the target and the site of elicitation of the alloimmune response.
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