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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p> Graphical abstract <p></p>

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Anti-CD19 chimeric antigen receptor T-cell therapy in a highly sensitized patient with focal and segmental glomerulosclerosis

  • 期刊论文

  • 发表日期：

    2025年7月16日

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  • 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

摘要

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.

Graphical abstract