2013 - IXA 2013 Congress
Joint Plenary Session: How can we overcome Immune Responses associated with Presensitization? - Optimal Regimen, Accommodation and B-Cell Tolerance
16.2 - Modification of B-cells in Alloimmunity
Presenter: Stanley, Jordan, Boston , United States
The introduction of B-cell-directed therapies for autoimmune diseases illuminated the biologic relevance of B cells in mediation of 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. These advances clearly have implications for patients receiving solid organ transplants, especially those who are ABO incompatible, sensitized to human leukocyte antigen (HLA) pre-transplant, or develop anti-HLA antibodies post-transplant.
B-cells play a central and critical role in the immunologic responses to invading pathogens. This is mediated through activation of the newly recognized T-helper/follicular (TFH) cells that are critical to stimulating B-cell progression to antibody producing plasma cells. This is arguably the most primal and essential function of the adaptive immune system. Dysregulation of B-cell immune responses are now recognized to be of critical importance in autoimmune diseases. This has led to a renewed and vigorous interest in modification of B-cell responses which have resulted in novel agents aimed at modification of B-cells and antibodies. The translational importance of this work to transplantation has resulted in advances in the prevention and treatment of alloantibody-induced injury.
Here, we will review the current and evolving agents developed for B-cell depletion or modulation and discuss their potential for modification of alloimmunity in transplant recipients. We will focus on data from humans and animal models in which B cells and antibodies are targeted to reduce inflammation in transplantation. This will include a review of the immunomodulatory drug intravenous immunoglobulin, anti-CD20 (rituximab) where more clinical experience has been reported. Finally, we will discuss emerging B-cell-directed therapies which include those directed at the B-cell activating factor of the tumor necrosis family/A proliferation inducing ligand, anti-CD22, newer anti-CD20 monoclonals, and evolving agents such as inhibitors of IL-21 and TFH generation as well as antibodies to the interleukin 6 receptor (Tocilizumab®).
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