Glycolysis Changes in Alloreactive Memory B Cells in Highly Sensitized Kidney Transplant Recipients Undergonig Desensitization Therapy

被引:0
作者
Noble, Johan [1 ,2 ,3 ]
Cabezas, Lara [1 ,2 ]
Truffot, Aurelie [3 ,4 ]
Dumolard, Lucile [2 ]
Jouve, Thomas [1 ,2 ]
Malvezzi, Paolo [1 ]
Rostaing, Lionel [1 ,2 ]
Dard, Celine [5 ]
Saas, Philippe [2 ,5 ]
Cravedi, Paolo [3 ]
Macek-Jilkova, Zuzana [2 ,6 ]
机构
[1] CHU Grenoble Alpes, Nephrol Hemodialysis Apheresis & Kidney Transplant, Grenoble, France
[2] Univ Grenoble Alpes, Inst Adv Biosci, CNRS, Inserm,CHU Grenoble Alpes, Grenoble, France
[3] Icahn Sch Med Mt Sinai, Translat Transplant Res Ctr, Dept Med, New York, NY 10029 USA
[4] Univ Hosp Grenoble, Virol Dept, Grenoble, France
[5] EFS, Rech & Dev, Grenoble, France
[6] CHU Grenoble Alpes, Hepatogastroenterol & Digest Oncol Dept, Grenoble, France
关键词
donor-specific antibody; desensitization; kidney transplantation; metabolism; memory B cells; glycolysis; DIFFERENTIATION; REJECTION; RISK;
D O I
10.3389/ti.2024.13029
中图分类号
R61 [外科手术学];
学科分类号
摘要
Despite the growing use of desensitization strategies, hyperimmune patients remain at high risk of antibody-mediated rejection suggesting that, even when donor-specific antibodies (DSA) are effectively depleted, anti-donor specific B cells persist. We included 10 highly sensitized recipients that underwent desensitization with plasmapheresis and B cell depletion prior to kidney transplantation. We quantified changes in DSA (luminex), total B-cell subsets (flow cytometry), anti-donor HLA B cells (fluorospot), and single-cell metabolism in serially collected samples before desensitization, at the time of transplant, and at 6 and 12 months thereafter. Desensitization was associated with a decrease in DSA and total memory B cell and naive B cell percentage, while plasma cells and memory anti-donor HLA circulating B cells persisted up to 12 months after transplant. At 12-month post-transplantation, memory B cells increased their glycolytic capacity, while proliferative KI67+ plasma cells modified their metabolism by increasing fatty acid and amino acid oxidation capacity and decreasing their glucose dependence. Despite effective DSA depletion, anti-donor B cells persist in kidney transplant recipients. Due to the reliance of these cells on glycolysis, glycolysis-targeting therapies might represent a valuable treatment strategy.
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页数:12
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