4.6 Review

Desensitization in Crossmatch-positive Kidney Transplant Candidates

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Clazakizumab for desensitization in highly sensitized patients awaiting transplantation

Ashley A. Vo et al.

Summary: This study aimed to evaluate the desensitization treatment effect for highly HLA-sensitized patients using clazakizumab. The results showed that desensitization treatment with clazakizumab could effectively reduce HLA antibody levels in highly sensitized patients, leading to a higher success rate of transplantation. Posttransplant, significant increases in T-reg and B-reg cells were observed, while antibody-mediated rejection also occurred.

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Immune responses following tocilizumab therapy to desensitize HLA-sensitized kidney transplant candidates

Thomas Jouve et al.

Summary: In highly sensitized kidney transplant candidates, tocilizumab as a monotherapy limited B cell maturation while having almost no effect on anti-HLA alloantibodies.

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Immortal Time-Bias-Corrected Survival of Highly Sensitized Patients and HLA-desensitized Kidney Transplant Recipients

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Summary: HLA desensitization is effective for highly sensitized patients in kidney transplantation, providing access to KT without adverse effects on patient or graft survival rates.

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Imlifidase Desensitization in Crossmatch-positive, Highly Sensitized Kidney Transplant Recipients: Results of an International Phase 2 Trial (Highdes)

Stanley C. Jordan et al.

Summary: This study investigated the efficacy and safety of imlifidase in converting a positive crossmatch test to negative in highly sensitized patients, allowing them to undergo kidney transplantation. Results showed that majority of transplanted patients achieved negative crossmatch within 24 hours after imlifidase treatment, with good kidney function and graft survival at 6 months.

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Dual and Opposite Costimulatory Targeting with a Novel Human Fusion Recombinant Protein Effectively Prevents Renal Warm Ischemia Reperfusion Injury and Allograft Rejection in Murine Models

Jordi Guiteras et al.

Summary: The study demonstrates the efficacy of HYBRI, a fusion protein containing CTLA4 and PD-L2 domains, in reducing inflammation and improving survival in rat kidney models of injury and transplant rejection. HYBRI shows promise as a potential therapeutic intervention for ischemia-reperfusion injury and solid organ transplantation.

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Efficacy of plasmapheresis and semi-selective immunoadsorption for removal of anti-HLA antibodies

Frederic Jambon et al.

Summary: This study compared the efficacy of PP and IA in removing anti-HLA antibodies, and found that IA had a stronger MFI reduction than PP in the extended apheresis protocol. For antibodies with an initial MFI < 3000, there was no superiority of IA over PP in the short protocol. Residual MFI predicted the effectiveness of four additional sessions for antibodies with an initial MFI >= 2000.

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Outcome of desensitization in human leukocyte antigen and ABO incompatible living donor kidney transplantation: Single center experience of first 200 incompatible transplants

Prashant Pandey et al.

Summary: The study compared the outcomes of renal transplant recipients across simultaneous ABO and HLA incompatibility barriers to those with ABO or HLA incompatibility alone, and found that patient and graft outcomes with incompatible transplants were not worse than those with compatible transplants.

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A Randomized Clinical Trial of Anti-IL-6 Antibody Clazakizumab in Late Antibody-Mediated Kidney Transplant Rejection

Konstantin Doberer et al.

Summary: This study was a phase 2 randomized trial evaluating the safety and efficacy of the anti-IL-6 antibody clazakizumab in late antibody-mediated rejection (ABMR) post-transplantation. Results showed that patients receiving clazakizumab had decreased donor-specific antibodies and modulated rejection-related gene-expression patterns.

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Human antiviral B cell responses: Emerging lessons from hepatitis B and COVID-19

Alice R. Burton et al.

Summary: Humoral immunity plays a critical role in resolving viral infections and providing protection, with factors shaping memory B cell responses allowing tailored development of efficient preventative vaccines. Lessons can be learned from different viral infections, including hepatitis B, regarding the diverse influences on humoral immunity.

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Comparison of three modalities of plasmapheresis on coagulation: Centrifugal, single-membrane filtration, and double-filtration plasmapheresis

Raphael Marlu et al.

Summary: The study found that DFPP was more effective in depleting high molecular-weight proteins compared to cTPE and mTPE, while all plasma exchange methods led to significant reductions in fibrinogen and FXIII.

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Impact of carfilzomib-based desensitization on heart transplantation of sensitized candidates

Roy Sriwattanakomen et al.

Summary: The study summarizes the experience of desensitization using carfilzomib in heart transplant candidates. Through multiple cycles of treatment, the level of HLA antibodies was significantly reduced, facilitating successful transplantation. The post-transplant survival rate was high, with a low occurrence of rejection episodes.

JOURNAL OF HEART AND LUNG TRANSPLANTATION (2021)

Article Urology & Nephrology

Presence of a survival benefit of HLA-incompatible living donor kidney transplantation compared to waiting or HLA-compatible deceased donor kidney transplantation with a long waiting time

Tai Yeon Koo et al.

Summary: HLA-incompatible living donor kidney transplantation may have better patient survival rate and survival benefit compared to waiting for HLA-compatible deceased donor kidney transplantation for sensitized patients with kidney failure in Korea.

KIDNEY INTERNATIONAL (2021)

Article Immunology

BLyS neutralization results in selective anti-HLA alloantibody depletion without successful desensitization

Divyansh Agarwal et al.

Summary: In highly sensitized kidney transplant candidates, BLyS blockade did not significantly reduce total anti-HLA allo-Ab levels but resulted in selective depletion of antibodies recognizing specific HLA allele specificities.

TRANSPLANT IMMUNOLOGY (2021)

Article Immunology

Donor/Recipient HLA Molecular Mismatch Scores Predict Primary Humoral and Cellular Alloimmunity in Kidney Transplantation

Maria Meneghini et al.

Summary: Molecular HLA mismatches between donors and recipients may impact the development of posttransplant T-cell alloimmunity and subsequent donor-specific cellular and humoral alloimmune activation. These immune responses are influenced by the degree of HLA molecular incompatibility between donors and recipients, as well as the pretransplant cellular immune status of the patients.

FRONTIERS IN IMMUNOLOGY (2021)

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Preformed T cell alloimmunity and HLA eplet mismatch to guide immunosuppression minimization with tacrolimus monotherapy in kidney transplantation: Results of the CELLIMIN trial

Oriol Bestard et al.

Summary: Personalizing immunosuppression in kidney transplant recipients with low immunological risk through biomarker-guided trials of tacrolimus monotherapy was found to be non-inferior to standard of care in terms of 6-month biopsy-proven acute rejection rates. However, recruitment challenges led to the early termination of the trial.

AMERICAN JOURNAL OF TRANSPLANTATION (2021)

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Fibrinogen reconstitution after therapeutic apheresis: Comparison of double-filtration plasmapheresis, plasma exchange, and immunoadsorption

Thomas Jouve et al.

Summary: Fibrinogen reconstitution after therapeutic apheresis is highly variable among patients and apheresis sessions. Different apheresis modalities have a significant impact on fibrinogen reconstitution, regardless of hemoconcentration.

JOURNAL OF CLINICAL APHERESIS (2021)

Review Immunology

HLA Desensitization in Solid Organ Transplantation: Anti-CD38 to Across the Immunological Barriers

Nizar Joher et al.

Summary: The presence of anti-HLA antibodies is a major barrier to solid organ transplantation. Desensitization protocols have shown improvements in transplantation rates but limitations still exist, prompting interest in new desensitization approaches focused on targeting alloimmune pathways beyond antibodies. Targeting CD38 to desensitize in the field of transplantation is an emerging concept worth further exploration.

FRONTIERS IN IMMUNOLOGY (2021)

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Apheresis Efficacy and Tolerance in the Setting of HLA-Incompatible Kidney Transplantation

Johan Noble et al.

Summary: This study evaluated the efficacy and tolerance of different techniques in removing donor specific antibodies in HLA-incompatible kidney transplant patients. The results showed that plasma exchange and other methods were effective in reducing antibody levels, allowing highly sensitized patients to undergo successful HLA-incompatible kidney transplantation with good safety outcomes.

JOURNAL OF CLINICAL MEDICINE (2021)

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Weak antibody response to three doses of mRNA vaccine in kidney transplant recipients treated with belatacept

Nathalie Chavarot et al.

Summary: Poor responses to mRNA COVID-19 vaccine were observed in kidney transplant recipients treated with belatacept, especially in those without prior COVID-19 history. However, patients with a history of COVID-19 developed a strong antibody response with high titers after vaccination. Further strategies are needed to improve protection in this population.

AMERICAN JOURNAL OF TRANSPLANTATION (2021)

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Outcomes at 3 years post-transplant in imlifidase-desensitized kidney transplant patients

Christian Kjellman et al.

Summary: Imlifidase is a cysteine proteinase that can cleave IgG and convert a positive crossmatch to negative, enabling kidney transplantation between previously HLA incompatible pairs. Studies have shown that recipients of imlifidase-enabled allografts have comparable outcomes to other highly sensitized patients undergoing HLA-incompatible transplantation.

AMERICAN JOURNAL OF TRANSPLANTATION (2021)

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Immunogenicity and Reactogenicity After SARS-CoV-2 mRNA Vaccination in Kidney Transplant Recipients Taking Belatacept

Michael T. Ou et al.

Summary: The study examined the immunogenicity after SARS-CoV-2 mRNA vaccines in kidney transplant recipients taking belatacept and those who are not. Belatacept use was associated with lower odds of having a positive post-D2 titer result, indicating the need for additional measures to protect kidney transplant recipients taking belatacept.

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Marginal Impact of Tocilizumab Monotherapy on Anti-HLA Alloantibodies in Highly Sensitized Kidney Transplant Candidates

Melanie Daligault et al.

Summary: The administration of tocilizumab as a monotherapy was found to significantly reduce dominant anti-HLA antibody sensitization in highly sensitized kidney transplant candidates. However, the decrease in mean fluorescence intensities was minor compared with the initial values, indicating that tocilizumab alone was not an effective desensitization method for these candidates.

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A prospective, iterative, adaptive trial of carfilzomib-based desensitization

Simon Tremblay et al.

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APRIL/BLyS Blockade Reduces Donor-specific Antibodies in Allosensitized Mice

Nancy A. Wilson et al.

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Daratumumab in Sensitized Kidney Transplantation: Potentials and Limitations of Experimental and Clinical Use

Jean Kwun et al.

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Alexandre Loupy et al.

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IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation

S. C. Jordan et al.

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Plasma cell survival in the absence of B cell memory

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Desensitization: Overcoming the Immunologic Barriers to Transplantation

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Immune Sensitization and Mortality in Wait-Listed Kidney Transplant Candidates

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Belatacept and Long-Term Outcomes in Kidney Transplantation

Flavio Vincenti et al.

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