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  • Highly polymorphic antigens expressed on the surface of cells

  • Have crucial roles in defense against foreign pathogens and in tumor immune surveillance

  • Antibodies against these antigens can develop as a result of pregnancy, transplantation, or blood transfusion

  • Human leukocyte antigen (HLA) sensitization adversely affects both access to and the outcomes of transplantation

  • Improved identification of HLA molecules and of the specificity of HLA antibodies has improved transplant graft survival

  • Desensitization of anti-HLA antibodies is essential to enable meaningful progress in the field of transplantation and increase the likelihood that a patient will receive a transplant offer.



  • Lower donor-specific antibody (DSA) levels at a range safe for transplantation

    • HLA antibodies below a positive complement-dependent cytotoxicity (CDC) antihuman globulin (AHG) cytotoxic crossmatch

    • Isohemagglutination immunoglobulin G (IgG) titers ≤16

Two Major Protocols

  • High-dose (1–2 g/kg) intravenous immunoglobulin (IVIg)

    • Protocols for both live and deceased donor transplant recipients

    • 2 g IVIg/kg infused monthly until:

      • Favorable crossmatch results

      • Four doses (main effect seen after the first dose)

    • Has a durable effect on HLA antibody that lasts for months and increases transplant rates

    • It may be more effective when combined with anti-CD20

    • Allows for transplantation of sensitized patients with no live donors

  • Plasmapheresis with low dose IVIg (100 mg/kg)

    • Hopkins protocol includes every-other-day plasmapheresis and low-dose IVIg

    • Plasmapheresis depletes HLA antibody, and IVIg prevents new endogenous synthesis

    • At least two posttransplant sessions

      • More sessions may be required based on DSA levels

      • Aim to achieve DSA strength below positive flow crossmatch

    • DSA levels rebound within days of discontinuing plasmapheresis if the transplant is not performed, so this is usually only an option for patients with live donors

    • DSA is often eliminated after posttransplant plasmapheresis, especially DSA to class I antigens

    • Twenty-five percent of patients will have an antibody-mediated rejection (AMR) after desensitization, and most of these AMR episodes respond to additional plasmapheresis and IVIg

    • Combining desensitization with kidney-paired donation can reduce the initial (pre-desensitization) strength (level) of DSAs and result in improved outcomes


  • Used selectively in high-risk donor–recipient combinations

    • Depletes memory B cells in secondary lymphoid tissues and peripheral blood

    • May prevent recall responses for which memory exists

    • Does not affect long-lived plasma cells that are residents in the bone marrow and do not express CD20

    • Splenectomy remains a rescue option in severe AMR (approximately 8% of cases)

Novel Approaches to Desensitization

  • Novel agents have shown great promise for both desensitization and the treatment of AMR when combined with standard-of-care therapies

  • Examples include:

    • Proteasome inhibitors such as bortezomib, which disrupt the normal intracellular protein degradation process

    • Complement inhibitors such as eculizumab, which binds to complement protein C5 and blocks both the classical and lectin pathways

    • Interleukin (IL-6) or IL-6 receptor blockers such as clazakizumab and ...

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