Abstract
IntroductionComparative data on synovial cell infiltrate and cytokine levels in anti citrullinated peptide/protein antibody (ACPA)-positive and ACPA negative rheumatoid arthritis (RA) patients are scarce. Our aim was to analyze synovial cell infiltrate and synovial fluid (SF) levels of cytokines in patients with RA according to the presence or absence of ACPA in serum.MethodsA cross-sectional study in a single center including consecutive RA patients was performed. Patients were defined as 'ACPA negative' if serum was negative to two different ACPAs [second generation commercial anti-cyclic citrullinated peptide antibodies (CCP2) and chimeric fibrin/filaggrin citrullinated antibodies]. Parallel synovial tissue (ST) biopsies and SF were obtained by knee arthroscopy. Synovial cell infiltrate and endothelial cells were analyzed by immunohistochemistry and SF levels of Th1, Th2, Th17 and pro-inflammatory cytokines by Quantibody(R) Human Array.ResultsA total of 83 patients underwent arthroscopy, with a mean age of 55.9 ± 12 years, and mean disease duration of 45 months (interquartile range, IQR 10.8 to 122). 62% were female and 77% were ACPA positive. No significant differences were found in clinical variables, acute phase reactants, synovial cell infiltrate or lymphoid neogenesis (LN) between ACPA positive and negative patients. However ACPA positive patients had significantly higher levels of IL-1β, IL-10, IL-17 F and CC chemokine ligand 20 (CCL-20) than ACPA negative patients.ConclusionsIn our cohort of patients with RA no significant differences were found in synovial cell infiltrate or synovial LN according to ACPA status. However, ACPA positive patients had higher levels of T-cell derived and pro-inflammatory cytokines than ACPA negative patients. As systemic and local inflammation was similar in the two groups, these findings support a distinct synovial physiopathology.
Highlights
Comparative data on synovial cell infiltrate and cytokine levels in anti citrullinated peptide/protein antibody (ACPA)-positive and ACPA negative rheumatoid arthritis (RA) patients are scarce
Our group demonstrated that a homemade ACPA Enzyme-linked immunosorbent assay (ELISA) test, using chimeric fibrin/ filaggrin citrullinated synthetic peptides (CFFCP) [8] had a high sensitivity and specificity for RA, and was able to detect some patients negative to commercial anti-cyclic citrullinated peptide antibodies (CCP2), the most common test used in clinical practice
rheumatoid factor (RF) was positive in 65 (78%) and ACPA in 64 (77%) patients; nine patients were positive for anti-CFFCP and negative for anti-Commercial anti-cyclic citrullinated peptide antibodies (CCP2), while four patients were positive for CCP2 but negative for anti-CFFCP
Summary
Comparative data on synovial cell infiltrate and cytokine levels in anti citrullinated peptide/protein antibody (ACPA)-positive and ACPA negative rheumatoid arthritis (RA) patients are scarce. There is evidence that RA patients positive for rheumatoid factor (RF) and anti-citrullinated peptide/protein antibodies (ACPA) have more severe disease and poorer outcomes [1]. Different citrullinated antigenic substrates have been developed in order to improve the sensitivity and specificity of ACPA tests for RA diagnosis, showing a good but not absolute correlation between them [7]. Our group demonstrated that a homemade ACPA ELISA test, using chimeric fibrin/ filaggrin citrullinated synthetic peptides (CFFCP) [8] had a high sensitivity and specificity for RA, and was able to detect some patients negative to commercial anti-cyclic citrullinated peptide antibodies (CCP2), the most common test used in clinical practice. Early RA patients who were positive for anti-CFFCP had a poor radiological outcome [9]
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