Ann Rheum Dis. 2026 Mar 17:S0003-4967(26)00088-9. doi: 10.1016/j.ard.2026.02.013. Online ahead of print.
ABSTRACT
OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by dysregulation of the adaptive and innate immunity. This study aimed to identify transcriptomic differences in neutrophils from patients with SLE and healthy individuals, analyse ex vivo adaptation dynamics, and evaluate the impact of chimeric antigen receptor (CAR) T-cell therapy on neutrophil transcriptomic profiles.
METHODS: Neutrophils were isolated via negative selection from 7 patients with SLE and 7 healthy individuals. RNA sequencing was performed to assess transcriptomic differences, ex vivo dynamics over 60 minutes, and responses to lipopolysaccharide (LPS) stimulation. In addition, longitudinal transcriptomic data from a patient with SLE undergoing KYV-101 anti-CD19 CAR T-cell therapy were evaluated.
RESULTS: We identified 258 differentially expressed genes consistently distinguishing SLE from healthy neutrophils; they spanned multiple clusters, enriched in interferon-related and DNA damage repair genes (upregulated), and ribosomal protein genes (downregulated). Ex vivo adaptation revealed shared activation pathways, such as NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) and apoptosis, in both groups. LPS stimulation highlighted overlapping inflammatory responses, demonstrating retained functional capacities in SLE neutrophils. Following CAR T-cell therapy of a patient with SLE, neutrophil transcriptomic profiles were realigned with healthy controls by 3 months posttreatment.
CONCLUSIONS: Neutrophils in SLE exhibit intrinsic, disease-specific transcriptomic alterations while sharing ex vivo adaptation dynamics with healthy individuals. The disease-specific alterations appear to be modifiable through targeted therapeutic intervention, as anti-CD19 CAR T-cell therapy resets neutrophil gene expression towards healthy patterns despite targeting B cells rather than neutrophils directly. These findings provide insights into SLE pathogenesis and highlight potential therapeutic strategies targeting both adaptive and innate immunity.
PMID:41850942 | DOI:10.1016/j.ard.2026.02.013