Serum Proteomic Signatures Before the Diagnosis of Rheumatoid Arthritis: Evolving Biologic Pathways and Specific Periods of Disease Development
Authors' conclusion
Autoantibodies and protein signatures evolve in distinct stages before a diagnosis of RA. Furthermore, protein biomarkers may identify biologic pathways relevant to specific stages.
Study context
- Population
- Patients with rheumatoid arthritis (RA) and matched controls without RA identified in the Department of Defense Serum Repository
- Participants
- 213 vs 215
- Comparison
- Patients before RA diagnosis vs matched controls without RA
- RAn = 213
- Controlsn = 215reference
- Outcome
- Serum proteins differentially expressed between patients and controls before RA diagnosis (longitudinal analyses; 197 proteins tested)
Methodological detailsmatched controls, linear mixed effect models
- Matched controls
- Linear mixed effect models
Main finding
As reported in the abstract
- Proteins differentially expressed between patients and controls
- 104
- Proteins differentially expressed ≤5 years before diagnosis
- 60
- Proteins differentially expressed within and before five years of diagnosis
- 42
- Proteins differentially expressed >5 years before diagnosis
- 2
- Kyoto Encyclopedia of Genes and Genomes pathways associated with these proteins
- 32
- Pathways enriched ≤5 years before diagnosis
- 21
Observational data: associations, not effects.
Further findings
RA-related autoantibodies (anti-CCP3, RF IgA, RF IgM) · ≤5 years before RA diagnosis
- Levels of anti-CCP3, RFIgA and RFIgM showed the greatest differences between patients and controls ≤5 years before RA diagnosis
Classification of a sample as from <3 years before RA diagnosis (ACPA-positive pre-RA samples and controls), AUC
- AUC, training set
- 0.78 (95% CI 0.67-0.89)
- AUC, validation set (0.68-0.92)
- 0.80
Original publication
Serum Proteomic Signatures Before the Diagnosis of Rheumatoid Arthritis: Evolving Biologic Pathways and Specific Periods of Disease Development. Arthritis Rheumatol. Published 13 May 2025. doi:10.
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