Introduction: Vascularized composite allotransplantation (VCA) is unique by presence of the skin in the allografts. Due to the high immunogenicity of skin and the presence of non-HLA polymorphic proteins, it has been hypothesized that skin specific antigens distinct from HLA are involved in allograft rejection. However, no such skin specific antigens in context of transplant rejection have been characterized in humans to date. Methods: We printed 190 different non-HLA antigens (skin specific proteins, nuclear antigens and non-HLA antigens known from solid organ transplantation) on custom protein microarrays and incubated them with serum samples from pre-transplant state and rejection episodes of 7 different VCA patients (5 face transplants and 2 hand transplants). Via fluorescent labeled secondary antibodies, we evaluated augmented (positive both pre- and post-transplantation) or de novo (negative pre-transplantation) antibody response in these patients. Results: 6 out of 7 patients displayed an elevated general IgG immune response towards the array proteins during a rejection episode compared to the pre-transplant state. 14 antibodies (8 skin specific and 6 nuclear antibodies) showed to be up-regulated during a rejection episode in at least 50% of the patients. The skin specific antigens were mainly attributable to hair follicles. In subsequent rejection episodes from the same patient, the antibody response appeared to be more pronounced with time. In three patients, we could detect de novo production of MICA antibodies. Conclusions: This is, to the best of our knowledge, the first report that indicates that skin specific antibodies correlate with acute rejection episodes in clinical VCA. Further research should determine whether sequential assessment of non-HLA antibodies could serve as non-invasive marker of rejection in VCA patients.

CITATION INFORMATION: Kollar B., Uffing A., Win T., Tasigiorgos S., Pomahac B., Quintana F., Riella L. Elevated Skin Specific Non-HLA Antibodies Correlate with Acute Rejection Episodes in Clinical VCA Am J Transplant. 2017;17 (suppl 3).

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