A research group led by Associate Professor Kentaro Ide and Professor Hideki Ohdan from the Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University has announced the development of a flexible desensitization therapy based on immune surveillance for kidney transplantation: "time-unrestricted, immune surveillance-guided desensitization therapy." This approach adjusts treatment content while monitoring the immune status of each patient. It has succeeded in achieving safe and favorable long-term outcomes, even for patients who were previously considered difficult to transplant. The results were published in the journal of the International Society of Nephrology, Kidney International Reports, on November 3.
Cells involved in DSA production include memory B cells, short-lived and long-lived plasma cells, and each cell needs to be controlled. Since rituximab is effective against memory B cells and short-lived plasma cells, if DSA is derived from short-lived plasma cells, desensitization is possible with rituximab alone. On the other hand, since it is ineffective against long-lived plasma cells, further administration of bortezomib is necessary. In this case, if rituximab and bortezomib are administered simultaneously, there is a risk of falling into an excessive immunosuppressed state, so bortezomib is administered after the mature B cells that disappeared after rituximab administration recover, but before the recovery of memory B cells.
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Donor-specific antibodies (DSAs) which react to the donated kidney may be produced in the body as a result of pregnancy, blood transfusion, or past transplantation. "Highly sensitized patients" who have DSAs are prone to strong rejection reactions, called antibody-mediated rejection, after transplantation due to DSA. This renders kidney transplantation difficult.
In contrast, "desensitization therapy" performed on highly sensitized patients utilizes rituximab (anti-CD20 monoclonal antibody) and immunoglobulin preparations to reduce the risk of rejection. However, this treatment method has shown limited effectiveness, highlighting the need for a more reliable and safe treatment method.
In this study, the researchers introduced "time-unrestricted desensitization therapy based on immune surveillance," which improves upon this desensitization therapy.
This new approach monitors the immune status of each patient in real time, and medications are administered in stages according to changes in immune response. In contrast, conventional methods relied on medications being administered on a fixed schedule.
Specifically, after suppressing B cells with rituximab, bortezomib (plasma cell inhibitor) or antithymocyte globulin was added as necessary, and this treatment was continued until DSA were no longer detectable.
As a result, DSA disappeared in 18 of 25 crossmatch-positive kidney transplant candidates (72%), achieving a state where transplantation was possible. The number of patients who developed antibody-mediated rejection after transplantation was 0. The graft survival rates - defined as the percentage of patients in whom the transplanted kidney functions normally in the body - at 5 and 10 years were favorable at 100% and 89%, respectively. No serious side effects were observed, confirming the treatment's safety.
As this treatment is personalized medicine that can be optimized according to immune response, application to other organ transplants and refractory immune diseases is also expected.
Ohdan commented: "Among patients who wish to undergo kidney transplantation, 'strong antibodies' are produced due to past pregnancy or blood transfusion, which can make transplantation difficult. This highly sensitized state has been a major obstacle for many years. In this research, by carefully evaluating the immune response of each patient while proceeding with treatment, we were able to open a new path to safely reach transplantation. In the future, we hope to develop treatment with shorter duration and fewer side effects, establishing it as medical care that can be delivered to patients nationwide."
Journal Information
Publication: Kidney International Reports
Title: Time-unrestricted, Immune Surveillance-Guided Desensitization Enables Kidney Transplantation in Highly Sensitized Patients
DOI: 10.1016/j.ekir.2025.10.026
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.