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BackgroundRheumatoid arthritis (RA) is characterized by synovium inflammation leading to joint destruction. No sensitive serum biochemical marker of synovial tissue activity is currently available. The aims of this study were to develop a new sensitive serum biochemical marker of synovium turnover and evaluate its performance in patients with RA.Methods We developed an enzyme-linked immunosorbent assay to measure synovial collagen fragments in serum (SynCol) using an antibody recognizing a specific 11 amino acid sequence from the triple helical portion of human type III collagen. The specificity of the antibody was evaluated by competitive inhibition with several collagen-related peptides. Immunohistochemistry was performed to localize the SynCol fragments in RA synovium. Serum SynCol was measured in patients with RA (n=66, 73% women, mean age 62 years, median disease activity score 28 (DAS 28) 2.6) participating in randomized clinical trials and in sex and age matched healthy controls (n=70, 76% women, mean age 59 years). ResultsThe SynCol ELISA demonstrated adequate analytical performances. Competitive inhibition experiments showed that the antibody used in the ELISA recognizes a neoepitope resulting from the cleavage of type III collagen molecules and also the homologous sequences of type IV collagen, but does not cross-react with intact type III and IV collagens. Immunohistochemistry of synovial tissue from a RA subject showed staining of SynCol fragments in the lining layer where destructive fibroblasts are localized and around blood vessels which are rich in type IV collagen. SynCol staining co-localized with matrix metalloproteinase 9 (MMP-9) immunostaining. Serum SynCol levels were significantly increased in patients with RA compared to healthy controls (+ 247 %, p 3.2, n=20) had levels which were 888 % (pConclusions The SynCol ELISA is a sensitive and precise assay measuring circulating type III and IV collagen degradation fragments originating from synovial tissue turnover. Serum SynCol levels are markedly increased in patients with RA, particularly in those with active disease. Trial Registration- Role of the ANS Dysregulation in the Persistence of Fatigue in Rheumatoid Arthritis Patients Treated with Anti-TNF (ANSRA) NCT02475486- Bone MicroArchitecture Abatacept (BMA2) NCT02675218- Impact of the Persistence of Inflammation at Doppler Ultrasound Level on the Structural Evolution of Erosion in Rheumatoid Arthritis Treated with Biotherapy. NCT02531061IRB for synovial tissue 2019-A02742-55 (Comité de Protection des Personnes Sud-Méditerranée I |
