Lupus & antiphospholipid syndrome

Central nervous system (CNS) immune remodelling in systemic lupus erythematosus (SLE) associated with anti-CD19 CAR-T therapy

Ann Rheum DisPublished Mechanistic study

Authors' conclusion

These findings suggest an association between CAR-T therapy and CNS immune remodelling in SLE, and provide cellular and molecular observations that may inform future studies of CNS immunity.

Study context

Population
Patients with refractory SLE treated with autologous anti-CD19 CAR-T therapy; plus independent baseline single-cell RNA sequencing and Olink samples47,222 cerebrospinal fluid (CSF) cells profiled · Olink samples 3
Participants
2 / 4 / 5
Comparison
Baseline vs D9 vs D60
  • Baselinen = 2reference
  • D9n = 4
  • D60n = 5
Outcome
CNS (CSF) immune remodelling after CAR-T therapy
Methodological detailslongitudinal, integrated single-cell RNA/TCR sequencing and Olink proteomics of CSF
  • Longitudinal
  • Integrated single-cell RNA/TCR sequencing and Olink proteomics of CSF

Main finding

As reported in the abstract

  • Dynamic CNS immune composition following CAR-T therapy, with notable changes in T cells
  • CAR-T cells detected in the CNS; predominantly proliferative and cytotoxic states at D9, memory- and exhaustion-associated states at D60
  • Endogenous CD8⁺ T cells: diverse effector subsets at day 9 (granzyme B (GZMB)⁺, NK-like, type I interferon (IFN)-responsive, human leukocyte antigen (HLA)⁺ granzyme H (GZMH)⁺), then predominance of memory and proliferating subsets at day 60
  • CD4⁺ T cells at day 9 enriched for type I IFN signalling
  • Extensive ligand-receptor interactions between myeloid populations and lymphocytes
  • Changes in TCR clonal diversity and dynamics following treatment

Original publication

CNS immune remodelling in SLE associated with anti-CD19 CAR-T therapy. Ann Rheum Dis. Published 23 July 2026. doi:10.1016/j.ard.2026.06.030

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