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Accommodation and related conditions in vascularized composite allografts

Platt, Jeffrey L.a,b; Kaufman, Christina L.c; Garcia de Mattos Barbosa, Mayaraa; Cascalho, Mariliaa,b

Current Opinion in Organ Transplantation: October 2017 - Volume 22 - Issue 5 - p 470–476
doi: 10.1097/MOT.0000000000000446
VASCULARIZED COMPOSITE ALLOTRANSPLANTATION: Edited by Christina L. Kaufman
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Purpose of review The outcome of vascularized composite allografts (VCA) often appear unrelated to the presence of donor-specific antibodies (DSA) in blood of the recipient or deposition of complement in the graft. The attenuation of injury and the absence of rejection in other types of grafts despite manifest donor-specific immunity have been explained by accommodation (acquired resistance to immune-mediated injury), adaptation (loss of graft antigen) and/or enhancement (antibody-mediated antigen blockade). Whether and how accommodation, adaptation and/or enhancement impact on the outcome of VCA is unknown. Here we consider how recent observations concerning accommodation in organ transplants might advance understanding and resolve uncertainties about the clinical course of VCA.

Recent findings Investigation of the mechanisms through which kidney allografts avert antibody-mediated injury and rejection provide insights potentially applicable to VCA. Interaction of DSA can facilitate replacement of donor by recipient endothelial cells, modulate or decrease synthesis of antigen, mobilize antigen that in turn blocks further immune recognition and limit the amount of bound antibody, allowing accommodation to ensue. These processes also can explain the apparent dissociation between the presence and levels of DSA in blood, deposition of C4d in grafts and antibody-mediated rejection. Over time the processes might also explain the inception of chronic graft changes.

Summary The disrupted tissue in VCA and potential for repopulation by endothelial cells of the recipient establish conditions that potentially decrease susceptibility to acute antibody-mediated rejection. These conditions include clonal suppression of donor-specific B cells, and adaptation, enhancement and accommodation. This setting also potentially highlights heretofore unrecognized interactions between these ‘protective’ processes.

aDepartment of Surgery

bDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan

cChristine M. Kleinert Institute for Hand and Microsurgery, Louisville, Kentucky, USA

Correspondence to Jeffrey L. Platt, MD, Professor of Surgery and Professor of Microbiology & Immunology, University of Michigan, A520B Medical Sciences Research Building I, 1150 W. Medical Center Drive, Ann Arbor, Michigan 48109-5656, USA. Tel: +1 734 615 7755; fax: +1 734 615 7141; e-mail: plattjl@umich.edu

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