Autoantibodies to Joint‐Related Peptides Are Associated With Onset of Rheumatoid Arthritis in Presymptomatic Seronegative Individuals
Authors' conclusion
These novel biomarkers can identify presymptomatic, seronegative individuals at high risk of RA onset and support their recruitment into trials for personalized prevention. Additionally, they distinguish early seronegative RA from OA with high specificity.
Study context
- Population
- Presymptomatic individuals who later developed rheumatoid arthritis (RA), at RA diagnosis, matched population controls and patients with osteoarthritis (OA); focus on anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF)-negative individualsthree cohorts
- Participants
- 518 / 241 / 530 / 287
- Comparison
- Presymptomatic individuals who later developed RA vs matched population controls and patients with OA
- Presymptomatic RAn = 518
- RA diagnosisn = 241
- Population controlsn = 530reference
- OAn = 287reference
- Outcome
- Performance of IgG autoantibodies against joint-related peptides (SeNe test) for anti-CCP and RF-negative RA
Methodological detailsnested case-control, multiplex bead-based flow immunoassay, principal component analysis, multivariable logistic regression
- Nested case-control
- Multiplex bead-based flow immunoassay
- Principal component analysis
- Multivariable logistic regression
Performance
As reported in the abstract
SeNe test associated with symptom onset within 2.5 years in anti-CCP and RF-negative individuals
13%
Specificity for RA vs OA
97%
95% CI 95%–99%
SeNe 2.0: anti-CCP and RF-negative presymptomatic individuals identified
16%
SeNe 2.0: specificity vs population controls
98%
Further findings
Presymptomatic autoantibody profiles (principal component analysis)
- Three distinct presymptomatic subgroups, suggesting early immune heterogeneity
- 3
SeNe 2.0 in anti-CCP and RF-negative presymptomatic individuals vs population controls
- Anti-CCP and RF-negative presymptomatic individuals identified
- 16%
- Specificity vs population controls
- 98%
SeNe 2.0 autoantibodies associated with presymptomatic state (multivariable model)
- SeNe 2.0 autoantibodies associated with presymptomatic state, including RF and anti-CCP
- Two of five
Original publication
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