Sensitization and desensitization of burn patients as potential candidates for vascularized composite allotransplantation

Abstract

Sensitization describes the acquired ability of the immune system to react to foreign human leukocyte antigens (HLA) by producing antibodies and developing memory cells. In the field of transplantation, recipient preformed HLA antibodies due to previous sensitization have been identified - beneath ABO incompatibility - as a major factor for acute graft rejection. Several reasons for sensitization have largely been studied, such as previous blood transfusions, pregnancies or former transplants. Recent studies indicate that the use of assist devices (e.g. ECMO) or cadaveric skin allotransplantation providing temporary coverage in burn patients may lead to additional sensitization. As vascularized composite allotransplantation (VCA) has become a rapidly advancing therapeutic option for reconstruction of complex tissue defects in burns, it seems even more important to become familiar with immunological principles and to be cautiously aware of both sources of sensitization and therapeutic concepts in burns avoiding sensitization. This may also include emergency VCAs in burn patients as potential strategy for early definitive reconstruction avoiding procedures triggering HLA antibody formation. We hereby provide an overview on current evidence in the field of pre- and peritransplant sensitization, followed by posttransplant strategies of desensitization and their potential impact on future treatments of burn patients.

Extensively burns patients are not unsuitable candidates to vascularized composite allotransplantations but require optimization in access to suitable transplants

“…5 Several desensitization techniques including intravenous immunoglobulins, plasmapheresis and immunoabsorption, increase the risks of infections and cancer incidence, represent a financial burden do not offer long lasting results. 6 Alternative options to increase the access to VCA are thus required such as dedicated allocation strategies with priority allocation program in immunized and hyperimmunized patients called acceptable mismatch program. 5 As a conclusion, extensively burns patients are not unsuitable candidates to VCA but their unavoidable broad and intense HLA sensitization mainly requires optimization in access to suitable transplants.…”

Emerging Implications for Extracellular Matrix-Based Technologies in Vascularized Composite Allotransplantation

“…Overall, VCA has achieved encouraging graft survival rates and functional outcomes. With few exceptions, patients who have complied with their treatment regimens have experienced satisfactory restoration of significant tissue deficits, improved functional and aesthetic outcomes, and reduced complications associated with these procedures [ 5 – 7 ].…”

Characteristics and Immunomodulating Functions of Adipose-Derived and Bone Marrow-Derived Mesenchymal Stem Cells Across Defined Human Leukocyte Antigen Barriers

“…The principle to replace “same with same” implies multiple important criteria to define suitable grafts for VCA recipients and their individual needs. In addition to age, sex, and skin color ( 3 ), general solid organ matching criteria such as cytomegalovirus status, patient sensitization ( 4 ), and human leukocyte antigen (HLA) typing play an important role in graft allocation and patient selection. The grade of HLA mismatch has been shown to increase the risk of acute rejection ( 5 ) in hand transplant patients and represents one of the biggest hurdles in VCA due to the shortage of donors.…”