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Immunopathology of rejection: do the rules of solid organ apply to vascularized composite allotransplantation?

Thaunat, Oliviera,b,c; Badet, Lioneld; Dubois, Valériee; Kanitakis, Jeanf; Petruzzo, Palminad; Morelon, Emmanuela,b,c

Current Opinion in Organ Transplantation: December 2015 - Volume 20 - Issue 6 - p 596–601
doi: 10.1097/MOT.0000000000000242
COMPOSITE TISSUE TRANSPLANTATION: Edited by Emmanuel Morelon
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Purpose of review As both the number of vascularized composite allotransplants (VCAs) recipients and the duration of their follow-up are limited, immunopathology of VCA rejection remains incompletely understood. VCAs have several immunological peculiarities, which make inaccurate a direct extrapolation of all rules established for solid organs.

Recent findings Despite their bone marrow content, VCA do not induce chimerism in recipient and are therefore not spontaneously tolerated. Skin compartment of VCA contains a high density of antigen-presenting cells (APCs), some with self-renewal capacity. Donor APCs are responsible for continuous direct allosensitization of recipient's T cells that explains the high incidence of skin T-cell-mediated rejection and their occurrence beyond 1 year.

Regenerative capability of the skin prevents the development of chronic rejection of this compartment as long as immunosuppression is maintained. In contrast, VCA can develop graft arteriosclerosis, which could be because of T cell and/or chronic antibody-mediated rejection (AMR). VCA recipients can indeed develop donor-specific antibodies (DSA). Whether DSA can also trigger acute AMR of VCA remains to be clarified.

Summary A better understanding of the specificities of the immunopathology of VCA rejection should pave the way for the rationalization of immunosuppressive strategies aiming at optimizing long-term outcome.

aHospices Civils de Lyon, Hôpital Edouard Herriot, Service de Transplantation, Néphrologie et Immunologie Clinique

bUniversité de Lyon

cINSERM, U1111

dHospices Civils de Lyon, Hôpital Edouard Herriot, Service d’Urologie et Transplantation

eEtablissement Français du Sang

fHospices Civils de Lyon, Hôpital Edouard Herriot, Service de Dermatologie, Lyon, France

Correspondence to Olivier Thaunat, MD, PhD, Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, 5 Place d’Arsonval, Lyon, France. Tel: +33 4 72 11 02 29; fax: +33 4 72 11 02 71; e-mail: olivier.thaunat@chu-lyon.fr

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