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In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients

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Immunosuppression in sensitized recipients.

Fabian Echterdiek¹, Joerg Latus, Vedat Schwenger

¹Department of Nephrology, Hypertension and Autoimmune Disorders, Klinikum Stuttgart, Stuttgart, Germany.

Current Opinion in Organ Transplantation

|December 10, 2019

Summary

Kidney transplants across human leukocyte antigen (HLA) and ABO barriers are increasing. New desensitization strategies and programs improve outcomes for highly sensitized recipients, despite risks of antibody-mediated rejection (AMR).

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Murine Model of Epicutaneously-Induced Immunomodulation

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Area of Science:

Nephrology
Immunology
Transplantation Medicine

Background:

Increasing demand for kidney transplants and a rise in sensitized recipients necessitate transplantation across human leukocyte antigen (HLA) and ABO barriers.
Transplanting across HLA and ABO barriers carries a significant risk of antibody-mediated rejection (AMR), potentially impairing graft and patient survival.

Purpose of the Study:

This review focuses on novel desensitization strategies and specialized programs designed for kidney allograft recipients who are highly sensitized.
To explore advancements in managing HLA- and ABO-incompatible kidney transplantations.

Main Methods:

Review of current literature on desensitization protocols for kidney transplantation.
Analysis of outcomes from ABO- and HLA-incompatible kidney transplantations.
Evaluation of dedicated programs for highly sensitized recipients and emerging therapeutic agents.

Main Results:

Rituximab-based desensitization for ABO-incompatible kidney transplants yields long-term survival comparable to ABO-compatible transplants.
HLA-incompatible living kidney transplantation does not consistently show a survival advantage over remaining on the waiting list for a compatible organ.
Dedicated programs, like the Eurotransplant Acceptable Mismatch program, and novel agents targeting AMR pathways show promise for HLA-incompatible transplants.

Conclusions:

Despite challenges, kidney transplantation in highly sensitized patients is feasible through dedicated programs and established desensitization agents.
Emerging drugs that specifically inhibit AMR molecular pathways offer new hope for improving graft outcomes in HLA-incompatible kidney transplantation.