Citrullinated antigens as C1q-binding and monoclonal rheumatoid factor (mRF)-binding peptides in synovial fluids from rheumatoid arthritis patients.
OBJECTIVE
Previous studies have demonstrated that immune complexes (ICs) may be involved in the pathogenesis of rheumatoid arthritis (RA). However, autoantigens contained in rheumatoid ICs remain to be elucidated. In the present study, we investigated whether the peptides captured by C1q and monoclonal rheumatoid factor (mRF), presumably associated with ICs, were citrullinated in synovial fluids from patients with RA.


METHODS
Sixteen rheumatoid arthritis synovial fluids (RASFs), 7 osteoarthritis synovial fluids (OASFs), and 20 sera from RA patients were used for experiments. ICs were measured using commercially available kits based on the C1q-binding (C1q-IC) and mRF-binding (mRF-IC) assays. Citrullination of the peptides captured by C1q and mRF was detected by anti-modified citrulline antibody (Senshu Ab) after chemical modification.


RESULTS
There was a significant correlation between levels of citrullination of C1q-binding peptides and those of mRF-binding peptides in RASFs (r=0.77), both of which were significantly higher than those in OASFs. No citrullinated Ags captured by C1q and mRF were detected in sera from patients with RA.


CONCLUSIONS
We have demonstrated the presence of citrullinated Ags as C1q- and mRF-binding peptides in RASF. We suggest that citrullinated Ags may contribute to the pathogenesis of RA through IC formation in the joint.
Third Department of Internal Medicine, Faculty of Medicine, Tokyo Medical University, 7-6-1 Nishishinjuku, Shinjuku, Tokyo, 160-0023 Japan. tsawada@tokyo-med.ac.jp
T
T
Sawada
T
T
Kanzaki
S
S
Hashimoto
A
A
Suzuki
R
R
Yamada
M
M
Odawara
K
K
Yamamoto
D000941:Antigens / Q000032:analysis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002956:Citrulline / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D010003:Osteoarthritis / Q000276:immunology; D012217:Rheumatoid Factor / Q000276:immunology*; D013582:Synovial Fluid / Q000737:chemistry* / Q000276:immunology
D000941:Antigens; D002352:Carrier Proteins; D007074:Immunoglobulin G; C007105:c1q-binding proteins; D002956:Citrulline; D012217:Rheumatoid Factor