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 6 publications

(2 citation statements)

References 98 publications

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“…Our findings highlight the clinical impact of the clearance of anti-HLA DSAs after renal transplantation. This is particularly important within the context of emerging new desensitization therapies [33,34]. However, factors leading to the clearance or persistence of preformed anti-HLA DSAs should be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Impact of Resolved Preformed, Persistent Preformed, and De Novo Anti-HLA Donor-Specific Antibodies in Kidney Transplant Recipients on Long-Term Renal Graft Outcomes

Gniewkiewicz

Czerwińska

Zielniok

et al. 2023

JCM

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The post-transplant evolution of antihuman leukocyte antigen donor-specific antibodies (anti-HLA DSAs) includes three clinical patterns: resolved preformed DSAs, persistent preformed DSAs, and de novo DSAs. The aim of this retrospective study was to analyze the impact of resolved preformed, persistent preformed, and de novo anti-HLA-A, -B, and -DR DSAs in kidney transplant recipients on long-term renal allograft outcomes. This is a post hoc analysis of the study conducted in our transplant center. One hundred eight kidney transplant recipients were included in the study. Patients were followed for a minimum of 24 months after allograft biopsy, which was performed 3 to 24 months after kidney transplantation. The identification of persistent preformed DSAs at the time of biopsy was the most significant predictor of the combined endpoint of the study (>30% decline in estimated glomerular filtration rate or death-censored graft loss; HR = 5.96, 95% CI 2.041–17.431, p = 0.0011), followed by the occurrence of de novo DSAs (HR = 4.48, 95% CI 1.483–13.520, p = 0.0079). No increased risk was observed in patients with resolved preformed DSAs (HR = 1.10, 95% CI 0.139–8.676, p = 0.9305). Patients with resolved preformed DSAs have similar graft prognoses as patients without DSAs, therefore, the persistence of preformed DSAs and development of de novo DSAs are associated with inferior long-term allograft outcomes.

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Section: Discussionmentioning

confidence: 99%

Impact of Resolved Preformed, Persistent Preformed, and De Novo Anti-HLA Donor-Specific Antibodies in Kidney Transplant Recipients on Long-Term Renal Graft Outcomes

Gniewkiewicz

Czerwińska

Zielniok

et al. 2023

JCM

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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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The Kidney Transplant Lottery: A Highly Sensitized Patient, Without Mismatches and Vein Thrombosis of the Graft; A Case Report

Esteves,

Grilo,

Fragoso

et al. 2024

Transplantation Proceedings

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

Cited by 6 publications

References 98 publications

Impact of Resolved Preformed, Persistent Preformed, and De Novo Anti-HLA Donor-Specific Antibodies in Kidney Transplant Recipients on Long-Term Renal Graft Outcomes

Impact of Resolved Preformed, Persistent Preformed, and De Novo Anti-HLA Donor-Specific Antibodies in Kidney Transplant Recipients on Long-Term Renal Graft Outcomes

Advances in desensitization for human leukocyte antigen incompatible kidney transplantation

The Kidney Transplant Lottery: A Highly Sensitized Patient, Without Mismatches and Vein Thrombosis of the Graft; A Case Report

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