Sjögren's disease & overlap diseases
Transcriptomic profiling of Sjögren’s disease salivary glands identifies signatures associated with both follicular and extrafollicular responses linked to rheumatoid factor and anti-La/SSB seropositivity
Authors' conclusion
Comprehensive SG bulk-RNA sequencing provided the first transcriptomic evidence of distinct RF and anti-La/SSB-driven SG transcriptomic signatures in patients with SjD with and without ELS.
Study context
- Population
- Patients with Sjögren's disease (SjD) and non specific-chronic-sialadenitis (sicca); labial salivary gland (SG) biopsies2 independent cohorts
- Participants
- 55 / 44 / 29
- Comparison
- SjD vs non specific-chronic-sialadenitis (sicca); SjD subsets by ectopic lymphoid structures (ELS) and rheumatoid factor (RF), anti-Ro/SSA and anti-La/SSB serostatus
- SjD (Queen Mary University of London (QMUL))n = 55
- Siccan = 44reference
- SjD (TRACTISS)n = 29
Methodological detailsbulk RNA-sequencing of labial SG, exploratory cohort and validation cohort
- Bulk RNA-sequencing of labial SG
- Exploratory cohort and validation cohort
Main finding
As reported in the abstract
- Unsupervised gene clustering confirmed clear transcriptome segregation between sicca and SjD
- In SjD, PCA: significant proportion of variability associated with RF-seropositivity, exceeding that associated with SG-ELS and anti-Ro/SSA seropositivity
- SjD-SG with ELS from RF, anti-Ro/SSA or anti-La/SSB positive patients: mainly genes associated with germinal centre formation
- SG without ELS from RF or double anti-Ro/anti-La seropositive patients (unlike seronegative or single anti-Ro/SSA): unique extrafollicular B-cell gene set associated with type-I interferon (IFN) via RIG-1 endogenous RNA (incl. viral) sensing pathway and E3-ubiquitin ligases
- Identified IFN genes showed strong positive correlations with serum RF levels in 2 independent cohorts (QMUL and TRACTISS)
Original publication
Transcriptomic profiling of Sjögren’s disease salivary glands identifies signatures associated with both follicular and extrafollicular responses linked to rheumatoid factor and anti-La/SSB seropositivity. Ann Rheum Dis. Published 21 August 2025. doi:10.
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