Isabella Guzzo, Marco Becilli, Andrea Cappoli, Pietro Merli, Raffaella Labbadia, Francesca Del Bufalo, Nicola M Tomas, Manuela Colucci, Tobias B Huber, Mattia Algeri, Marco Andreani, Francesco Emma, Franco Locatelli
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引用次数: 0
Abstract
Background: High panel reactive antibody (PRA) titers are a significant challenge for patients undergoing kidney transplantation. Currently, no desensitization protocol has proven effective in preventing mid- and long-term graft loss. In the present study, we used anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in an attempt to reduce PRA in a highly sensitized patient. The role of this therapy in preventing focal segmental glomerulosclerosis (FSGS) recurrence was also evaluated.
Methods: An 18-year-old girl with primary kidney failure secondary to FSGS failed a first kidney transplant at age 4 years due to disease recurrence. Despite being listed in a special program for hyperimmune patients, she had not been offered a new kidney. She received a single infusion of anti-CD19 CAR T cells after lymphodepletion therapy. Anti-human leukocyte antigens (HLA) antibody titers were monitored before therapy and monthly thereafter.
Results: PRA titers decreased progressively during the first 6 months after CAR T-cell therapy. Unexpectedly, after 5.5 months, the patient was offered a cadaveric kidney that was fully matched for HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ at the antigen level. However, she developed an early relapse of FSGS for which she started plasmapheresis, which prevented further monitoring of PRA titers.
Conclusions: This case shows that a single infusion of anti-CD19 CAR T cells can induce a durable reduction of anti-HLA antibodies in highly sensitized patients. However, profound B-cell depletion did not prevent FSGS relapse.
背景:高面板反应性抗体(PRA)滴度是肾移植患者面临的重大挑战。目前,没有脱敏方案被证明能有效预防中长期移植物损失。在本研究中,我们使用抗cd19嵌合抗原受体(CAR) t细胞治疗,试图减少高度敏感患者的PRA。该疗法在预防局灶节段性肾小球硬化(FSGS)复发中的作用也被评估。方法:一名18岁的女孩继发于FSGS的原发性肾衰竭,在4岁时因疾病复发未能进行第一次肾移植。尽管她被列入了一个针对过度免疫患者的特殊项目,但她并没有得到一个新的肾脏。在淋巴细胞清除治疗后,她接受了抗cd19 CAR - T细胞的单次输注。治疗前和治疗后每月监测抗人白细胞抗原(HLA)抗体滴度。结果:在CAR - t细胞治疗后的前6个月,PRA滴度逐渐下降。出乎意料的是,在5.5个月后,患者被提供了一个在抗原水平上与HLA-A、HLA-B、HLA-C、HLA-DR和HLA-DQ完全匹配的尸体肾脏。然而,她的FSGS早期复发,并开始血浆置换,这阻碍了进一步监测PRA滴度。结论:该病例表明,在高度敏感的患者中,单次输注抗cd19 CAR - T细胞可以诱导抗hla抗体的持久降低。然而,严重的b细胞耗尽并不能防止FSGS复发。
期刊介绍:
International Pediatric Nephrology Association
Pediatric Nephrology publishes original clinical research related to acute and chronic diseases that affect renal function, blood pressure, and fluid and electrolyte disorders in children. Studies may involve medical, surgical, nutritional, physiologic, biochemical, genetic, pathologic or immunologic aspects of disease, imaging techniques or consequences of acute or chronic kidney disease. There are 12 issues per year that contain Editorial Commentaries, Reviews, Educational Reviews, Original Articles, Brief Reports, Rapid Communications, Clinical Quizzes, and Letters to the Editors.