Lupus & antiphospholipid syndrome
Dysregulation of U12 ‐Type Splicing in Lupus Neutrophils
Authors' conclusion
Impaired U12-dependent splicing may contribute to neutrophil dysfunction in SLE, potentially via defective oxidative burst and altered immune regulation.
Study context
- Population
- Patients with systemic lupus erythematosus (SLE) and healthy controls
- Comparison
- SLE low-density granulocytes (LDGs) vs SLE and HC normal-density granulocytes (NDGs)
Methodological detailsbulk RNA sequencing (RNA-seq), rMATS splicing analysis, independent long-read RNA-seq validation
- Bulk RNA-seq
- rMATS splicing analysis
- Independent long-read RNA-seq validation
Main finding
As reported in the abstract
- CYBA expression reduced in SLE LDGs (n = 11) vs SLE and HC NDGs (n = 6), at levels resembling chronic granulomatous disease neutrophils
- Impaired NADPH oxidase (Nox) activity in SLE LDGs (n = 7 SLE, n = 12 HC)
- Broad down-regulation of U12 intron-containing genes in SLE LDGs, suggesting minor spliceosome dysfunction
- Increased U12-type intron retention and widespread splicing defects (exon skipping, mutually exclusive exon use) in genes such as GBP5, MAEA and STX10
- Abnormalities validated in independent long-read RNA-seq data set from SLE PBMCs
- Splicing disruptions correlated with disease activity and autoantibody profiles
Original publication
Dysregulation of U12 ‐Type Splicing in Lupus Neutrophils. Arthritis Rheumatol. Published 19 March 2026. doi:10.
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