13. Donor-Specific Antibodies in Vascularized Composite Allotransplantation: a Multicenter Study.

Résumé fourni par la source

Introduction: Vascularized Composite Allotransplantation (VCA), including upper extremity transplantation (UET) and face transplantation, requires immunosuppression to prevent allosensitization and subsequent rejection. Donor-specific anti-HLA antibodies (DSA) are recognized contributors to vascular rejection and poorer graft outcomes in solid organ transplantation. This study evaluates the prevalence, characteristics, and clinical implications of DSA in VCA recipients. Methods: Thirty-seven VCA recipients from six international centers were included. A total of 402 pre-transplant and follow-up sera were screened for DSA using a centralized Single Antigen Bead assay. Clinical and histological data, including rejection episodes and graft vasculopathy, were collected and analyzed. Results: The 37 patients were grafted between 2000 and 2019: 23 upper extremity transplantations (UETs), 13 face transplantations and 1 patient with simultaneous UET and face transplantation. There were 29 men and 8 women with a median age at transplantation of 32.5 years. Thirty-one recipients were evaluable for DSA: 17 had no DSA, 2 had preformed DSA and unclassifiable de novo anti-HLA antibodies, 3 had preformed DSA only, 8 had de novo DSA, 1 had both preformed and de novo DSA. The incidence of de novo DSA did not significantly differ between UET and face recipients, with an average onset of 9 months post-transplantation. Pretransplant DSA primarily targeted class I HLA, whereas de novo DSA predominantly targeted class II HLA. Both preformed and de novo DSA displayed comparable disappearance kinetics. DSA positivity was associated with a significantly higher incidence of chronic rejection and a trend towards increased graft vasculopathy. In one face recipient who developed de novo DSA and graft vasculopathy leading to graft loss, histological analysis revealed microvascular inflammation features, including lamellation, endothelial cell swelling, and intravascular cells in capillaries and venules. Conclusions: Humoral immunization is a common event following VCA, in both face and UET recipients, and is associated with chronic rejection and likely contributes to graft vasculopathy. However, mechanistic studies are needed to confirm the causal role of DSA in graft damage in VCA recipients.

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