The rheumatoid arthritis citrullinome is enriched in antigenic complement proteins
Authors' conclusion
This analysis of the circulating citrullinome in RA reveals the generation of citrullinated complement proteins that serve as autoantigens.
Study context
- Population
- Anti-citrullinated protein antibody (ACPA)+ Rheumatoid Arthritis (RA) patients, controls and unaffected first-degree relatives
- Participants
- 10 / 10 / 31 / 26 / 31
- Comparison
- ACPA+ RA vs controls; ACPA+ first-degree relatives (FDR) and RA vs ACPA- FDR
- RAn = 10
- Controlsn = 10reference
- ACPA- FDRn = 31reference
- ACPA+ FDRn = 26
- RA (validation)n = 31
- Outcome
- Circulating RA citrullinome (citrullinated serum proteins by mass spectrometry)
Methodological detailsunsupervised proteomic analysis, mass spectrometry, in-silico modelling (Alphafold 3.0)
- Unsupervised proteomic analysis
- Mass spectrometry
- In-silico modelling (Alphafold 3.0)
Main finding
As reported in the abstract
Citrullinated serum proteins (RA citrullinome)
- Higher expression of complement proteins in the RA citrullinome
- RA vs Controls: P = 0.02
- RA vs Controls: P = 0.019
Further findings
| Outcome | P value |
|---|---|
| Cit-C9 IgG immune complexesACPA+ FDR vs ACPA- FDR · elevated | P < 0.0001 |
| Cit-C9 IgG immune complexesRA (validation) vs ACPA- FDR · elevated | P < 0.0001 |
| Autoantibodies to cit-C9ACPA+ FDR vs ACPA- FDR · higher | P = 0.01 |
| Autoantibodies to cit-C9RA (validation) vs ACPA- FDR · higher | P = 0.002 |
Cit-C9 IgG immune complexes
- Cit-CFI immune complexes not elevated
Reactivity to linear peptides of cit/homocit C9
- Enriched in RA vs controls
In-silico structure of cit-C9
- Structural changes to monomeric and multimeric structure of cit-C9
Original publication
The rheumatoid arthritis citrullinome is enriched in antigenic complement proteins. Arthritis Res Ther. Published 28 January 2026. doi:10.
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