Lupus & antiphospholipid syndrome
Blood RNA-sequencing across the continuum of antinuclear antibodies (ANA)-positive autoimmunity reveals insights into initiating immunopathology
Authors' conclusion
ANA positivity, irrespective of clinical trajectory, is profoundly dysregulated and transcriptomically closer to SLE than to healthy immune function. Metabolic derangements and IFN-I activation occur early in the ANA+ preclinical phase and associated with diverging transcriptomic profiles which distinguish subsequent clinical evolution.
Study context
- Population
- ANA+ subjects with non-diagnostic symptoms, healthy subjects and patients with systemic lupus erythematosus (SLE)35 ANA+ subjects
- Participants
- 15 / 20 / 15 / 18
- Comparison
- ANA+ progressors vs non-progressors vs healthy subjects vs SLE
- ANA+ progressorsn = 15
- ANA+ non-progressorsn = 20
- Healthyn = 15reference
- SLEn = 18
- Outcome
- Blood immune cell transcriptional signatures associated with subclinical ANA positivity and progression or non-progression to SLE
- Follow-up
- Baseline; progression at 12 months
Methodological detailsbulk RNA-sequencing of PBMCs, weighted gene co-expression network analysis, deconvolution of cell subsets
- Bulk RNA-sequencing of PBMCs
- Weighted gene co-expression network analysis
- Deconvolution of cell subsets
Main finding
As reported in the abstract
- ANA+ subjects: extensive transcriptomic dysregulation vs healthy controls, with reduced CD4+ naïve T-cells and resting NK cells but higher activated dendritic cells
- B-cell lymphopenia evident in SLE but not ANA+ subjects
- Two-thirds of dysregulated genes common to ANA+ progressors and non-progressors
- ANA+ progressors: elevated modular interferon signature, constituent genes inducible by both IFN-I and IFN-II in vitro
- Baseline downregulation of mitochondrial oxidative phosphorylation complex I components significantly associated with progression to SLE, not directly correlated with IFN modular activity
- Non-progressors: more diverse cytokine profiles
Original publication
Blood RNA-sequencing across the continuum of ANA-positive autoimmunity reveals insights into initiating immunopathology. Ann Rheum Dis. Published 30 September 2024. doi:10.
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