Extracorporeal photopheresis: from solid organs to face transplantation

Composite tissue allotransplantations (CTA), were introduced with the first successful hand transplantation and are now a part of reconstructive surgery armamentarium. These reconstructive procedures for non life-threatening indications remain rare due to adverse effects of the associated lifelong immunosuppressive therapy. Indeed, despite recent progress, immunosuppressive therapies remain non-specific to the type of donor and still bear significant risks of serious side effects. Extracorporeal photopheresis (ECP), also called photochemotherapy, has been introduced in the composite tissue allotransplantation field as a part of acute rejection treatment in face transplantations. ECP has been performed after solid organ transplantations as a supportive therapy for acute rejection episodes. It has also been used to treat graft versus host diseases, which can occur after bone marrow or stem cell transplantations. ECP is also used to treat dermatologic diseases, such as cutaneous T-cell lymphoma, or autoimmune diseases, such as scleroderma or pemphigus vulgaris. The principle of ECP is to induce leucocyte apoptosis with UVA radiation after their presentation by psoralens. These leucocytes are immediately re-infused into the patient, where they undergo early apoptosis. Following apoptosis, the leucocytes are engulfed by macrophage or other antigen-presenting cells, such as immature dendritic cells, in an anti-inflammatory cytokine environment. The anti-inflammatory cytokine secretion pattern, with a switch from TH1 to TH2 for CD4+ lymphocytes, and the engulfment by immature cells without co-stimulatory molecules induces anergy, by deleting effector T-cells that responded to the presented antigens. An increase in regulatory T-cells (T-regs) is also induced after ECP and may contribute to allograft acceptance by the recipient. ECP has already been used for the great majority of solid organ transplantations to cure acute rejection episodes or in an attempt to prevent or cure chronic rejections, such as bronchitis obliterans, which occurs after lung transplantation. Considering composite tissue allotransplantations, ECP was used in two face transplantations after the occurrence of second rejection episodes triggered by viral infections. ECP therapy, associated with maintenance immunosuppressive therapy and doses of methylprednisolone, and the control of viral infection, succeeded to reverse the rejection process without the development of other side effects. Despite the fact that the mechanism of action of ECP has not been fully elucidated, this therapy could be a useful supportive therapy during the treatment of acute rejection episodes in composite tissue allotransplantations. In this review, we introduce the interest of ECP implementation in CTA in face allotransplantations.