Current approaches to treatment of antibody-mediated rejection

Abstract

Antibody-mediated rejection (AMR) has recently been recognized as a significant and unique form of rejection that is not amenable to treatment with standard immunosuppressive medications aimed at modification of T-cell function. Recent interest in AMR and the role of B cells in rejection has been aided by the concomitant discovery that C4d staining of renal biopsy tissue is strongly associated with AMR and a poor prognosis, and the emergence of desensitization protocols for treatment of highly human leukocyte antigen (HLA)-sensitized patients. Treatment options include: (i) the use of high-dose intravenous immunoglobulin (IVIG) which works by blocking anti-HLA antibody activity and through complement inhibition, (ii) the use of Rituxan (anti-CD20 chimeric antibody) to deplete B cells and interfere with antigen-presenting cell (APC) activity of B cells subsequently decreasing T-cell activation, and (iii) the use of plasmapheresis (PE) + anti-cytomegalovirus (CMV) immunoglobulin G (IgG) or IVIG in lower doses. This protocol removes deleterious anti-HLA antibodies and may also allow complexing of anti-HLA with anti-idiotypes in the anti-CMV IgG. Although early, data support the efficacy of all three approaches. Many centers are now designing protocols that utilize a combination of all three agents. In summary, recent advances in the diagnosis and treatment of AMR has allowed for significant improvements in outcomes of a condition usually associated with rapid graft failure. However, much work needs to be done to better understand the immunologic processes leading to AMR and how current therapies can be best used to effectively prevent and treat it.