The Role of Donor-Specific HLA Alloantibodies in Liver Transplantation

Abstract

The impact of donor‐specific HLA alloantibodies (DSA) on short‐ and long‐term liver transplant outcome is not clearly defined. While it is clear that not all levels of allosensitization produce overt clinical injury, and that liver allografts possess some degree of alloantibody resistance, alloantibody‐mediated adverse consequences are increasingly being recognized. To better define the current state of this topic, we assembled experts to provide insights, explore controversies and develop recommendations for future research on the consequences of DSA in liver transplantation. This article summarizes the proceedings of this inaugural meeting. Several insights emerged. Acute antibody‐mediated rejection (AMR), although rarely diagnosed, is increasingly understood to overlap with T cell–mediated rejection. Isolated liver allograft recipients are at increased risk of early allograft immunologic injury when preformed DSA are high titer and persist posttransplantation. Persons who undergo simultaneous liver–kidney transplantation are at risk of renal AMR when Class II DSA persist posttransplantation. Other under‐appreciated DSA associations include ductopenia and fibrosis, plasma cell hepatitis, biliary strictures and accelerated fibrosis associated with recurrent liver disease. Standardized DSA testing and diagnostic criteria for both acute and chronic AMR are needed to distil existing associations into etiological processes in order to develop responsive therapeutic strategies.

Advancing Transplantation

“…105,106 This resilience is facilitated by numerous mechanisms, but several are of critical importance. The liver's size, affording it a 100-fold microvasculature compared to the kidney, regenerative capacity, ability to secrete soluble class I antigen, and the existence of hypocomplementemia (secondary to liver dysfunction) serve to mollify the effects of preformed DSAs.…”

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

“…The implementation of immune modulation protocols including high doses of IVIg, plasmapheresis and potent immunosuppressive drugs resulted in attenuation of the humoral alloimmune response and in acceptable outcome in highly sensitized kidney and heart transplants [127][128][129][130][131][132][133] . The prognostic relevance of a positive T-lymphocytotoxic crossmatch in LT is, however, still discussed controversially [127,[134][135][136][137][138][139][140][141][142][143][144] . Originally, the liver was considered to be less susceptible to immunologic attacks.…”

Biomarkers in blood for individualization of the pharmacotherapy with immunosuppressive drugs after transplantation of solid organs

“…Immunosuppressive drugs may, perhaps, differ in terms of the risk of developing DSA, because during treatment with the mTOR inhibitor everolimus, there were more DSA and humoral rejections than those observed with cyclosporine [69] . Also, in heart and liver transplantations, the incidence of de novo DSA is associated with a poorer graft survival [70,71] . An antibody-mediated rejection was the most common cause of organ failure in kidney transplant patients in a study performed by Sellar é s et al [72] .…”