Donor-specific antibodies in vascularized composite allotransplantation: A multicenter study

Vascularized Composite Allotransplantation (VCA) requires immunosuppression to prevent allosensitization and subsequent allograft rejection. This study evaluated the prevalence, characteristics, and clinical implications of donor-specific antibodies (DSA) in VCA recipients. Thirty-seven VCA recipients (median age 32.5 years) from six international centers, grafted between 2000 and 2019, were studied. They included 23 upper extremity transplantations (UETs), 13 face transplantations and one patient with simultaneous UET and face transplantation. A total of 402 pre-transplant and follow-up sera were screened for DSA using a centralized assay. Among the 31 evaluable recipients, DSA appeared in a range of time between 7 and 2740 days post-transplantation with a median time of 360 days. The cumulative incidence of de novo DSA was 26% at five years and 48% at ten years. The incidence of de novo DSA did not differ between UET and face recipients. Both preformed and de novo DSA displayed comparable disappearance kinetics. A higher incidence of chronic rejection was observed in patients with DSA when an MFI cutoff of 500 was used (46.7% vs. 17.6% in patients with and without DSA, respectively), which became significant (p = 0.02) when the cutoff was increased to 1000. In conclusion, humoral immunization is a common event following VCA. DSA positivity was associated with chronic rejection and graft vasculopathy. Further mechanistic studies are needed to confirm the role of DSA in VCA rejection.