Epitopes targeted by autoantibodies in presymptomatic individuals predict early rheumatoid arthritis
Authors' conclusion
Antibody responses to certain citrullinated epitopes are associated with lower disease activity in treatment-naïve early RA and appear years before symptom onset of RA.
Study context
- Population
- Presymptomatic individuals, population controls in Sweden, and treatment-naïve early rheumatoid arthritis (RA) patients (NORD-STAR)
- Participants
- 520 / 530 / 690
- Comparison
- Anticitrullinated protein antibody (ACPA) responses to citrullinated or native ENO1 or PAD4 peptides in presymptomatic individuals vs population controls, and their association with early RA disease activity
- Presymptomatic individualsn = 520
- Population controlsn = 530reference
- NORD-STARn = 690
- Outcome
- ACPA responses to novel peptides predicting clinical outcomes (CRP, DAS28 and its components tender joint count (TJC), SJC, erythrocyte sedimentation rate (ESR)) of treatment-naïve early RA
Methodological detailsbead-based multiplex flow immunoassay, validation cohort (NORD-STAR)
- Bead-based multiplex flow immunoassay
- Validation cohort (NORD-STAR)
Performance
As reported in the abstract
ACPA responses to ENO1 and PAD4 peptides and RA severity
- In the presymptomatic (0.2-5 years before onset) and early RA stage, ACPA responses to several ENO1 and PAD4 peptides associated with less severe RA (lower C-reactive protein (CRP) and disease activity score (DAS28) and its components)
- In presymptomatic individuals, ACPA responses widely predicted lower disease activity in early RA, more pronounced in 5 selected peptides
Further findings
Time course of ACPA response in presymptomatic stage
- Time-dependent increase of ACPA response to citrullinated peptides towards onset
Early RA, rheumatoid factor (RF)-negative subgroup
- Association more pronounced in RF-negative patients based on lower swollen joint count (SJC)
Monoclonal ACPA binding
- Monoclonal ACPAs displayed distinct binding patterns to ENO1 and PAD4 peptides
Original publication
Epitopes targeted by autoantibodies in presymptomatic individuals predict early rheumatoid arthritis. Ann Rheum Dis. Published 9 May 2025. doi:10.
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