Drugs Targeting Alloantibodies and Alloreactive B Cells

As we have learned more about the importance of allo-antibodies in mediating acute and perhaps chronic rejection, therapies targeting antibodies and B cells that were developed for other diseases are now being used in transplant patients. For example, plasmapheresis is sometimes used to treat acute antibody-mediated rejection. In this procedure, a patient's blood is pumped through a machine that removes the plasma but returns the blood cells to the circulation. In this way, circulating antibodies, including pathogenic alloreactive antibodies, can be removed. Intravenous immune globulin (IVIG) therapy, which is used to treat several, often antibody-mediated, inflammatory diseases, is also being applied in the setting of acute antibody-mediated rejection. In IVIG therapy, pooled IgG from normal donors is injected intravenously into a patient. The mechanisms of action are not fully understood but likely involve binding of the injected IgG to the patient's Fc receptors on various cell types, thereby reducing alloantibody production and blocking effector functions of the patient's own antibodies. IVIG also enhances degradation of the patient's antibodies by competitively inhibiting their binding to the neonatal Fc receptor (see Chapter 12). A monoclonal antibody specific for the B cell surface protein CD20 very effectively depletes mature B cells from the circulation and secondary lymphoid organs. Anti-CD20 has been used for treatment of B cell lymphomas and for autoimmune diseases and is now in clinical trials for treatment of antibody-mediated allograft rejection. These antibody and B cell targeted therapies have been used in combination to effectively treat antibody-mediated rejection.

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