Guzzo Isabella, Becilli Marco, Cappoli Andrea, Merli Pietro, Labbadia Raffaella, Del Bufalo Francesca, Tomas Nicola M, Colucci Manuela, Huber Tobias B, Algeri Mattia, Andreani Marco, Emma Francesco, Locatelli Franco
Division of Nephrology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Department of Hematology/Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Pediatr Nephrol. 2025 Jul 16. doi: 10.1007/s00467-025-06884-1.
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.
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.
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.
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.
高群体反应性抗体（PRA）滴度对接受肾移植的患者来说是一项重大挑战。目前，尚无脱敏方案被证明能有效预防中长期移植肾丢失。在本研究中，我们使用抗CD19嵌合抗原受体（CAR）T细胞疗法，试图降低一名高度致敏患者的PRA水平。还评估了该疗法在预防局灶节段性肾小球硬化（FSGS）复发中的作用。
一名18岁的女孩，因FSGS继发原发性肾衰竭，4岁时首次肾移植因疾病复发失败。尽管她被列入了针对高敏患者的特殊项目，但仍未获得新的肾脏。在淋巴细胞清除疗法后，她接受了单次抗CD19 CAR T细胞输注。在治疗前及之后每月监测抗人白细胞抗原（HLA）抗体滴度。
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，5.5个月后，为该患者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。然而，她出现了FSGS早期复发，为此她开始进行血浆置换，这使得无法进一步监测PRA滴度。
该病例表明，单次输注抗CD19 CAR T细胞可使高度致敏患者的抗HLA抗体持久降低。然而，深度B细胞清除并不能预防FSGS复发。
