Impact of donor-specific antibodies in reconstructive transplantation

Abstract

For many devastating injuries and tissue defects where conventional reconstruction is not possible, reconstructive transplantation such as hand and face transplantation has become a viable alternative. This novel approach allows for improved restoration of appearance, anatomy and function not feasible by other available treatment options. However, clinical management of these injuries prior to transplantation frequently requires multiple blood transfusion or skin grafts resulting in the formation of alloantibodies (anti-HLA IgG Abs) and a high degree of sensitization. The role of donor-specific antibodies (DSA) and mechanisms of antibody-mediated rejection (AMR) in reconstructive transplantation are still largely unknown. Thus there is an imminent need to develop a better understanding of the mechanisms related to DSA and AMR after reconstructive transplantation. In this review, we will define the role of DSA and mechanisms of AMR in reconstructive transplantation and compare them to established measures and treatment concepts in solid organ transplantation.

Keywords::

• antibody-mediated rejection
• chronic rejection
• desensitization
• donor-specific antibodies
• face transplantation
• hand transplantation
• kidney-paired donation
• plasmapheresis
• reconstructive transplantation
• vascularized composite allotransplantation

Financial and competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • The role of donor-specific antibody (DSA)-mediated rejection in vascularized composite allografts (VCA) has never been broadly investigated and limited data is available.

• • In solid organ transplantation (i.e., kidney transplants), over 40% of patients on a waiting list are sensitized and antibody-mediated rejection in such sensitized patients is responsible for high percentages of graft loss.

• • VCA (i.e., face or hand transplant) recipients often undergo several blood transfusions and coverage with allogeneic skin grafts, leading to sensitization.

• • Production of antibodies anti-MHC class I and II are responsible for antibody-mediated rejection.

• • Currently the presence of DSA results in exclusion of such patients as VCA recipients.

• • The Johns Hopkins Transplant Program has lead the way to desensitization protocols that have achieved successful transplantation of highly sensitized patients.

• • DSA trigger complement-mediated tissue injury and C4d deposition.

• • Inclusion of sensitized recipients to VCA transplant programs may be possible following tailored desensitization regimens in selected centers with long-standing experience in the field.