Recent advances in allograft vasculopathy. Issue 1 (February 2017)

• Record Type: Journal Article
• Authors: Merola, Jonathan; Jane-wit, Daniel D.; Pober, Jordan S.
• Is Part Of: Current opinion in organ transplantation. Volume 22:Issue 1(2017:Feb.)
• Page Start: 1
• Page End: 7
• Publication Date: 2017-02
• Subjects: allograft vasculopathy -- alloimmunity -- chronic rejection -- transplantation; Transplantation of organs, tissues, etc -- Periodicals; Immunosuppression -- Periodicals; Transplantation immunology -- Periodicals; 617.954
• DOI: 10.1097/MOT.0000000000000370
• Languages: English
• ISSNs: 1087-2418

Abstract

Abstract : Purpose of review: Despite considerable advances in controlling acute rejection, the longevity of cardiac and renal allografts remains significantly limited by chronic rejection in the form of allograft vasculopathy. This review discusses recently reported mechanistic insights of allograft vasculopathy pathogenesis as well as recent clinical evaluations of new therapeutic approaches. Recent findings: Although adaptive immunity is the major driver of allograft vasculopathy, natural killer cells mediate vasculopathic changes in a transplanted mouse heart following treatment with donor-specific antibody (DSA). However, natural killer cells may also dampen chronic inflammatory responses by killing donor-derived tissue-resident CD4 + T cells that provide help to host B cells, the source of DSA. DSA may directly contribute to vascular inflammation by inducing intracellular signaling cascades that upregulate leukocyte adhesion molecules, facilitating recruitment of neutrophils and monocytes. DSA-mediated complement activation additionally enhances endothelial alloimmunogenicity through activation of noncanonical NF-κB signaling. New clinical studies evaluating mammalian target of rapamycin and proteasome inhibitors to target these pathways have been reported. Summary: Allograft vasculopathy is a disorder resulting from several innate and adaptive alloimmune responses. Mechanistic insights from preclinical studies have identified agents that are currently being investigated in clinical trials.