Sentinel Skin Allograft for Monitoring of Composite Tissue Transplants Rejection

In contrast to visceral solid-organ transplants, a vascularized composite tissue allograft (CTA) is not a single tissue, and is histologically heterogeneous. It is a neurovascularized module of nonvital tissues which include structural, functional and aesthetic units. CTAs are composed of a large spectrum of ectodermal tissues: epidermis and epidermal derivatives such as nails and hair, nerves and mesodermal tissues such as dermis, muscles, bones, articular cartilage, ligaments, tendons and paratenon and other supportive and connective tissues, adipose tissue, vessels. In addition there are hematopoietic tissues and cells from bone marrow and lymph nodes and these latter elements are immunocompetent. Each tissue has differing antigenicity, displays different antigen expression and presentation mechanisms. As a result, CTAs elicit nonsynchronized immune responses, of differing intensity, among their tissue components. So far only 135 CTA transplantations were carried out on human patients: 68 hand transplantations (49 patients), 12 abdominal wall transplantations, 9 bone and vascularized articulations transplantations, 7 peripheral nerves, 2 tendons, 23 larynxes, 1 right abdominal muscle, 1 tongue, a lobe made of the cephalic cervical skin and 2 ears, and 11 faces. The transplantation of a composite tissue allograft is only justified when excellent functional outcome can be achieved. This aim is more important for CTAs then for organ allografts as the procedure is not lifesaving and lifelong immunosuppressive therapy, with its associated risks and side effects, is difficult to justify. Even mild and reversible rejection episodes can decrease the chance of a favorable outcome. Skin is an important component of a CTA and is the most immunogenic of the component tissues. The skin is more sensitive to rejection than any other tissues or visceral organ, and the primary reason is probably its unique immunologic defense function, with its special intrinsec antigenic and immunologic properties. Boss et al. identified these properties as "the skin immune system” and demonstrate, that the skin is not only the largest organ in the body but is itself an immunologic effector organ, with almost half its cells belonging or related to the immune system (especially the large quantity of dendritic cells within epidermis and dermis). For CTAs the best marker of rejection is by visual and histopathological examination of the skin, as it is the skin that is first involved in the rejection process. Skin is an important component of a CTA and is the most immunogenic of the component tissues. The skin is more sensitive to rejection than any other tissues or visceral organ, and