Diagnosis and management of antibody-mediated rejection: current status and novel approaches

A Djamali, D B Kaufman, T M Ellis, W Zhong, A Matas, M Samaniego, A Djamali, D B Kaufman, T M Ellis, W Zhong, A Matas, M Samaniego

Abstract

Advances in multimodal immunotherapy have significantly reduced acute rejection rates and substantially improved 1-year graft survival following renal transplantation. However, long-term (10-year) survival rates have stagnated over the past decade. Recent studies indicate that antibody-mediated rejection (ABMR) is among the most important barriers to improving long-term outcomes. Improved understanding of the roles of acute and chronic ABMR has evolved in recent years following major progress in the technical ability to detect and quantify recipient anti-HLA antibody production. Additionally, new knowledge of the immunobiology of B cells and plasma cells that pertains to allograft rejection and tolerance has emerged. Still, questions regarding the classification of ABMR, the precision of diagnostic approaches, and the efficacy of various strategies for managing affected patients abound. This review article provides an overview of current thinking and research surrounding the pathophysiology and diagnosis of ABMR, ABMR-related outcomes, ABMR prevention and treatment, as well as possible future directions in treatment.

Keywords: Antibody-mediated rejection; complement C4d; donor-specific antibodies; phenotype.

© 2014 The Authors American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.

Figures

Figure 1
Figure 1
Mechanisms of donor-specific antibody-mediated endothelial injury in renal allografts. Anti-MHC antibodies may either result in direct injury to the capillary endothelium or in indirect injury via complement fixation or recruitment of inflammatory cells with Fc receptors. In cases with donor-specific antibodies that lack C4d deposition, endothelial injury and cellular recruitment could be important mediators. Poly, polymorphonuclear cell. Reproduced with permission from Farkash and Colvin .
Figure 2
Figure 2
Acute and chronic definitions of ABMR based on C4d positivity. ABMR, antibody-mediated rejection; ATN, acute tubular necrosis; DSA, donor-specific antibodies; IF, immunofluorescence; IFTA, interstitial fibrosis and tubular atrophy; IHC, immunohistochemistry; PTC, peritubular capillary. Reproduced with permission from Mengel et al .
Figure 3
Figure 3
The natural history of phenotype 2 ABMR. ABMR, antibody-mediated rejection; DSA, donor-specific antibodies; IFTA, interstitial fibrosis and tubular atrophy; TG, transplant glomerulopathy. Reproduced with permission from Wiebe et al .
Figure 4
Figure 4
Therapeutic modalities for ABMR. ABMR, antibody-mediated rejection; APC, antigen-presenting cell; IVIG, intravenous immunoglobulins.

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Source: PubMed

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