Novel insights in the clinical management of hyperimmune patients before and after transplantation

Grimaldi, Vincenzo; Pagano, Mario; Moccia, G.; Maiello, Ciro; Rosa, Paride De; Napoli, Claudio

doi:10.1016/j.crimmu.2023.100056

Cited by 4 publications

(1 citation statement)

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“…Our desensitization protocols have included anti-CD20 (rituximab or biosimilar equivalents) as a fundamental component, acting as potent B-cell depleting agents and likely beneficial to prevent primary sensitization and recall antibody responses by memory B-cell depletion [18,[20][21][22]24,25]. Comprehensive reviews of the applications of IVIG and anti-CD20 agents for desensitization have been published [26][27][28][29][30]. Anti-CD20 therapeutics have also advanced, including the development of, Obinutuzumab (type II anti-CD20), which demonstrated clinical superiority to rituximab in treatment of B-cell lymphoma and systemic lupus erythematosus [31].…”

Section: Targeting B-cellsmentioning

confidence: 99%

Advances in desensitization for human leukocyte antigen incompatible kidney transplantation

Vo,

Ammerman,

Jordan

2023

Current Opinion in Organ Transplantation

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Purpose of review Human leukocyte antigen (HLA) sensitization is a major barrier to kidney transplantation induced by exposure to alloantigens through pregnancy, blood product exposure and previous transplantations. Desensitization strategies are undertaken to improve the chances of finding compatible organ offers. Standard approaches to desensitization include the use of plasmapheresis/low dose intravenous immunoglobulin (IVIG) or high dose IVIG plus anti-CD20. However, current methods to reduce HLA antibodies are not always successful, especially in those with calculated panel reactive antibody 99–100%. Recent findings Newer desensitization strategies such as imlifidase [immunoglobulin G (IgG) endopeptidase] rapidly inactivates IgG molecules and creates an “antibody-free zone”, representing an important advancement in desensitization. However, pathogenic antibodies rebound, increasing allograft injury that is not addressed by imlifidase. Here, use of anti-IL-6R (tocilizumab) or anti-interleukin-6 (clazakizumab) could offer long-term control of B-memory and plasma cell DSA responses to limit graft injury. Agents aimed at long-lived plasma cells (anti-CD38 and anti-BCMAxCD3) could reduce or eliminate HLA-producing plasma cells from marrow niches. Other agents such as complement inhibitors and novel agents inhibiting the Fc neonatal receptor (FcRn) mediated IgG recycling will likely find important roles in desensitization. Summary Use of these agents alone or in combination will likely improve the efficacy and durability of desensitization therapies, improving access to kidney transplantation for immunologically disadvantaged patients.

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