Sjögren's disease & overlap diseases
Human hypofunctional NCF1 variant aggravates salivary gland immunopathology in Sjögren’s disease by promoting switched memory B-cell recruitment and long-lived plasma cell differentiation
Main finding · Risk of SjD (Chinese and European Americans)Result — go to the resultOdds ratio 2.58Authors' conclusion
Low NCF1 activity increases the risk of severe SSA+ SjD by driving switched memory B-cell trafficking and IgG+ plasma cell differentiation, revealing targetable pathways in SSA+ SjD.
Study context
- Population
- Patients with Sjögren's disease (SjD) and controls in Chinese and European American case-control cohorts; SSA+ SjD patients for PBMC and minor salivary gland (MSG) analyses
- Comparison
- NCF1-H90 allele carriers vs non-carriers
- Outcome
- Association between NCF1-H90 and SjD
Methodological detailscase-control cohorts, longitudinal observational cohort, cytometry by time-of-flight, single-cell RNA sequencing, retrospective belimumab-treated cohort
- Case-control cohorts
- Longitudinal observational cohort
- Cytometry by time-of-flight
- Single-cell RNA sequencing
- Retrospective belimumab-treated cohort
Main finding
Risk of SjD (Chinese and European Americans)
Odds ratio
2.58
Pmeta = 1.15E-55
As reported in the abstract
Further findings
| Outcome | OR |
|---|---|
| Risk of SSA+ SjD (subgroup)NCF1-H90 · Chinese | 3.37 |
| Risk of SSA+ SjD (subgroup)NCF1-H90 · European Americans | 2.60 |
Baseline clinical features, homozygous H90 SjD (longitudinal cohort)
- Lower complement C4 and higher labial salivary gland biopsy, ESSDAI and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) scores
- Sustained elevated ESSDAI and ESSPRI during follow-up with decreased survival
Switched memory B cells in peripheral blood mononuclear cells (PBMCs) by H90 copies (0, 1, 2)
- Dose-dependent decreases in switched memory B cells
Response to belimumab, homozygous H90 (retrospective SSA+ female cohort)
- Significantly greater improvement in ESSDAI, C4 levels and serum SSA+ IgG levels
Original publication
Human hypofunctional NCF1 variant aggravates salivary gland immunopathology in Sjögren’s disease by promoting switched memory B-cell recruitment and long-lived plasma cell differentiation. Ann Rheum Dis. Published 18 April 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →