Hua Su1, Chun-Yun Zhang1, Ji-Hong Lin2, Hans-Peter Hammes2, Chun Zhang1. 1. Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2. 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Abstract
BACKGROUND: Antibody-mediated rejection (ABMR) following kidney transplant is closely associated with poor prognosis of the recipients. Long-lived plasma cells (LLPCs) produce alloantibodies as long as life time and play a crucial role in ABMR. SUMMARY: LLPCs generate from germinal centers and reside in survival niches in the bone marrow as well as the inflamed tissues. They are the main and long-term source of the antibodies. LLPCs mediate ABMR via the generation of preformed antibodies in sensitized patients and de novo antibodies after transplantation. They have been acknowledged as the leading causes of ABMR; however, LLPCs are insensitive to traditional immunosuppressive therapy that removes B cells. Strategies targeting LLPCs, such as antithymocyte globulin, proteasome inhibitors as well as monoclonal antibodies, are promising methods to persistently and thoroughly clear the entire PC pool. KEY MESSAGE: LLPCs play an important role in ABMR by producing alloantibodies continually, and targeting LLPCs might be a novel and effective approach against ABMR.
BACKGROUND: Antibody-mediated rejection (ABMR) following kidney transplant is closely associated with poor prognosis of the recipients. Long-lived plasma cells (LLPCs) produce alloantibodies as long as life time and play a crucial role in ABMR. SUMMARY: LLPCs generate from germinal centers and reside in survival niches in the bone marrow as well as the inflamed tissues. They are the main and long-term source of the antibodies. LLPCs mediate ABMR via the generation of preformed antibodies in sensitized patients and de novo antibodies after transplantation. They have been acknowledged as the leading causes of ABMR; however, LLPCs are insensitive to traditional immunosuppressive therapy that removes B cells. Strategies targeting LLPCs, such as antithymocyte globulin, proteasome inhibitors as well as monoclonal antibodies, are promising methods to persistently and thoroughly clear the entire PC pool. KEY MESSAGE: LLPCs play an important role in ABMR by producing alloantibodies continually, and targeting LLPCs might be a novel and effective approach against ABMR.
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