Lupus & antiphospholipid syndrome
Differential molecular signatures in response to CD19-CAR T cell therapy compared with conventional pharmacotherapy in systemic lupus erythematosus
Authors' conclusion
CD19-CAR T cell therapy induces substantial suppression of key immunological pathways involved in SLE, including complement activation and type I interferon responses, accompanied by a metabolic reprogramming. Molecular profiles of remission after CD19-CAR T cell therapy differ from those induced by conventional SLE pharmacotherapy, suggesting more profound CD19-CAR T cell-induced biological alterations.
Study context
- Population
- Patients with systemic lupus erythematosus (SLE)
- Participants
- 7 / 30 / 31
- Comparison
- CD19-CAR T cell therapy vs standard pharmacotherapy
- CD19-CAR Tn = 7
- Standard pharmacotherapy remissionn = 30reference
- Rituximab, belimumab or cyclophosphamiden = 31reference
- Outcome
- Molecular pathway alterations
Methodological detailstranscriptomic comparison, single-cell RNA sequencing (pseudo-bulk), whole-blood transcriptome, Pathway analysis using Functional Analysis of Individual Microarray Expression and gene set enrichment analysis
- Transcriptomic comparison
- Single-cell RNA sequencing (pseudo-bulk)
- Whole-blood transcriptome
- Pathway analysis using Functional Analysis of Individual Microarray Expression and gene set enrichment analysis
Main finding
As reported in the abstract
- CD19-CAR T-induced remission: marked suppression of complement activation, type I interferon, DNA damage response (DDR) and cell death pathways vs remission after conventional pharmacotherapy, with upregulation of lipid metabolism pathways
- vs rituximab and belimumab: greater downregulation of type I/II interferon, DDR and chemokine pathways with CD19-CAR T
- vs cyclophosphamide: greater suppression of interferon, mitochondrial and mammalian target of rapamycin signalling pathways with CD19-CAR T
Original publication
Differential molecular signatures in response to CD19-CAR T cell therapy compared with conventional pharmacotherapy in systemic lupus erythematosus. Ann Rheum Dis. Published 23 July 2025. doi:10.
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