Introduction: The clinical significance of donor-specific anti-HLA antibodies (DSAs) in vascularized composite allotransplantation is not clear, even though their occurrence has been reported by several teams. The aim of the present multicenterc study was to assess the incidence of DSAs in upper extremity (UET) and face transplanted patients and their influence on patient outcomes.

Methods and Results: Pre- and post-transplantation sera of 37 patients (23 UET, 13 face transplantations and 1 simultaneous UET and face transplantation) were screened in a single laboratory using a solid phase assay. The recipients included 29 men and 8 women, median age was 33 years. Their immunosuppressive treatment, number of HLA mismatches, number of acute rejection (AR) episodes with Banff score, occurrence of graft vasculopathy, chronic rejection and graft loss were collected. In addition, the histological impact of DSA was studied in a small cohort of these patients. For each patient from our cohort with de novo DSA, we randomly selected 2 biopsies taken before and 3 biopsies after the appearance of DSA. DSA were detected in 43.2% of the recipients (16/37), including 6 patients who had presented preformed DSA. The intensity of recipient humoral alloimmune response was estimated using the MFI of positive beads in solid-phase assay. This showed variability both among recipients and among the different DSA specificities of the same patient. From an overall perspective, the alloimmune response was not very strong (median MFI 1413). Donor and recipient age and gender as well as the immunosuppressive treatment were not statistically different between the recipients who developed DSA and those who did not do it. Interesting the number of AR and Banff score did not influence DSA occurrence. No significant correlation between the presence of DSA and chronic rejection, graft vasculopathy or graft loss was found. Five patients with DSA developed chronic rejection and 4 of them graft vasculopathy. In addition, 2 recipients with DSA experienced several episodes of atypical rejections. Longitudinal assessment showed that almost all preformed DSA disappear over time and almost 50% of de novo DSA also in those patients who developed chronic rejection and/or graft vasculopathy with graft loss. There were 5 cases of graft loss and 3 of which had developed DSA during their follow-up. The histopathological study performed on skin sections obtained after the appearance of DSA (routinely-stained and immunolabelled for CD34) did not show significant influx of inflammatory cells into the dermal capillaries endothelial, cell swelling, or microthrombosis.

Conclusion: The study confirms that VCA is a sensitizing event for recipients. However, the evolution of DSA over time seems rather heterogeneous. Pre-formed DSAs tend to disappear rapidly and potentially no longer be deleterious, contrary to de novo DSA whose evolution and pathogenicity remain to be elucidated. Longer follow-up will allow to better assess the outcomes of the patients who developed DSA.