Sensitization in Heart Transplantation: Emerging Knowledge: A Scientific Statement From the American Heart Association

Abstract

Sensitization, defined as the presence of circulating antibodies, presents challenges for heart transplant recipients and physicians. When present, sensitization can limit a transplantation candidate’s access to organs, prolong wait time, and, in some cases, exclude the candidate from heart transplantation altogether. The management of sensitization is not yet standardized, and current therapies have not yielded consistent results. Although current strategies involve antibody suppression and removal with intravenous immunoglobulin, plasmapheresis, and antibody therapy, newer strategies with more specific targets are being investigated.

Desensitizing highly sensitized heart transplant candidates with the combination of belatacept and proteasome inhibition

“…Transplant candidates sensitized to HLA antigens wait longer for transplant, have increased waitlist mortality, and remain at risk of rejection after transplant. 1,2 Contemporary desensitization strategies focus on eliminating antibodies (plasmapheresis and more recently Ides) and/or the precursor cells responsible for their production (proteasome inhibitors and anti-CD20 antibodies). [3][4][5][6] Although promising in select cases, their efficacy is variable and frequently complicated by rebound due to homeostatic proliferation (compensatory B cell proliferation in response to the depletion of antibody-producing cells).…”

Successful Desensitization by Post-Centrifugal Plasma Filtration in Two Highly Sensitized Heart and Lung Transplant Recipients

“…Within one week of IVIg administration, a 33% decrease in panel-reactive Ab was observed in heart transplant recipients, and a > 80% reduction in cytotoxicity was achieved with repeated doses [1]. Recently, therapeutic monoclonal Abs have been used to prevent graft rejection [3]. Rituximab, a chimeric anti-CD20 monoclonal Ab, has no effect on plasma cells, but does affect B cells [3].…”

“…Recently, therapeutic monoclonal Abs have been used to prevent graft rejection [3]. Rituximab, a chimeric anti-CD20 monoclonal Ab, has no effect on plasma cells, but does affect B cells [3]. Therapeutic plasma exchange (TPE) also decreases intravascular IgG levels, with an efficacy comparable to that of IVIg, but it requires a longer treatment period.…”

“…The presence of donor-specific antibodies (DSAs) not only increases the incidence of antibody-mediated rejection (AMR) but also leads to other complications, such as increased frequency of high-grade T cell-mediated rejection, chronic lung allograft dysfunction, bronchiolitis obliterans syndrome, cardiac allograft vasculopathy, and poor allograft survival in heart and lung transplant recipients [ 1 – 3 ]. Sensitized patients have a lower five-year survival rate than non-sensitized patients (65% vs. 74%), and rejection occurs more acutely and severely in the former than in the latter [ 3 , 4 ]. We describe successful desensitization using post-centrifugal plasma filtration (PCPF) in two heart and lung transplant recipients with multiple DSAs.…”

“…Intravenous immunoglobulin (IVIg; 1–2 g/kg) and anti-thymocyte globulin (0.75–1.5 mg/kg) were administered as induction therapy. Depending on the patient condition, steroids and bortezomib may be administered [ 3 – 5 ]. IVIg therapy is at the core of most desensitization protocols and provides protection against infectious complications [ 6 ].…”