Novel Therapeutic Approaches to Allosensitization and Antibody-Medicated Rejection

Modification of pathogenic antibodies for autoimmune diseases illuminated the biologic relevance of B cells, plasma cells and pathogenic antibodies in autoimmunity. They have also rejuvenated interest in how B cells mediate multiple effector functions that include antibody production, antigen presentation to T cells, costimulation and the production of immune stimulating and immune modulatory cytokines. Repurposing these drugs from autoimmunity and cancer immunotherapy has yielded important advancements in the care of ABMR patients and novel drug development aimed at HLA desensitization have recently emerged. We now stand on an important threshold that promises many advances in the care of our allosensitized patients. We hope these initial advances will encourage basic scientist, clinical investigators, industry, National Institutes of Health (NIH), our academic societies and the FDA to continue support of these important objectives. These advances clearly have implications for sensitized patients receiving solid organ transplants and ABMR treatment. Modification of alloimmunity and alloantibodies will also have relevance to xenotransplantation where the xenoantibodies present a formidable obstacle to advancement of this important therapy. Working together, we can advance transplant therapeutics where biologic agents are likely to play novel and important roles. Here we discuss novel drugs emerging in this area. Refer Correspondence to: Stanley C. Jordan, M.D.,FASN, FAST, Director, Nephrology & Transplant Immunology, Medical Director, Kidney Transplant Program, Cedars-Sinai Medical Center, 8900 Beverly Blvd., West Hollywood, CA. 90048, Professor of Pediatrics & Medicine, David Geffen School of Medicine at UCLA. Email: sjordan@cshs.org. Fax: 310-423-6369 Competing interest S.C.J. received grant support from Hansa Medical, CSL-Behring, Vitaeris, and Genentech and is a consultant for Hansa Medical, CSLBehring, and Genentech. E.H., A.V, J.C., A.P., S.S., R.N, M.T., K.L, S.L, N.A. have no disclosures to report. Authors Contributions S.C.J. participated in the conception, design, and supervision of work, acquisition and analysis of data, preparation of draft, critical revisions to, and final approval of the manuscript. N.A. conducted the literature evaluation, preparation of draft and revisions to the manuscript. M.T. participated in the conception, design and performance of work, acquisition and analysis of data, and contribution to the preparation of the manuscript. E.H., A.V, J.C., A.P., S.S., R.N, K.L, S.L. participated in the conception, design and performance of work, and contribution to the preparation of the manuscript. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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