Background There is strong evidence that rheumatoid arthritis (RA) ACPA positive patients have a different clinical outcome than those that are ACPA negative. However, among these patients there is limited data about the synovial fluid (SF) and synovial cells differences.
Objectives To analyse the synovial cellular infiltrate and the SF Th1, Th2, Th17/IL-23 and pro-inflammatory cytokine pattern in a cohort of patients with RA according to the presence or absence of ACPA in the serum.
Methods A cross-sectional study in a single center was done and included 300 consecutive RA patients. We defined a patient as ACPA negative if their serum was negative to 2 different ACPA antibodies [commercial CCP2 and chimeric fibrin/filaggrin citrullinated antibodies]. Synovial biopsies and SF were obtained by knee arthroscopy. Cellular infiltrate in lining and sublining layers was analyzed by immunohistochemistry and digital analysis, including neutrophils (CD15), macrophages (CD68), mast-cells (CD117), endothelial cells (CD31/34) as well as presence of lymphoid neogenesis [follicular aggregate grade ≥.2, T/B cell segregation and high endothelial venules (MECA-79 epitope)]. SF concentrations of Th1, Th2, Th17 and pro-inflammatory cytokines were determined by Quantibody® Human Th17 Array (RayBiotech, GA, USA).
Results Eighty three patients underwent arthroscopy due to active disease. The mean age at the time of arthroscopy was 56±12 yrs, with a mean disease duration of 73±76 months. Most of the patients were female (63%) with erosive disease (73%). RF was positive in 78% and ACPA in 64 (77%) patients. There were no clinical differences in terms of disease activity, remission rates, erosive disease or biologic treatment, among ACPA positive and ACPA negative patients. Immunohistochemical analysis did not achieve a significant difference between the 2 groups. Also, there were no differences in presence of lymphoid neogenesis or number and grade of follicular aggregates according to ACPA status. SF analysis was available in 51 patients (40 ACPA positive/11 negative). ACPA positive patients had significantly higher levels of IL-1b, IL-10, IL-4, IL-17F and CCL-20 than ACPA negative patients (Table). There were no significant differences in the other cytokines including GM-CSF, IFNg, IL-2, IL-5, IL-6, IL-12p70, IL-13, IL-17, IL-21, IL-22, IL-23, TGFb, TNFa and TNFb.
Conclusions In our cohort of patients with RA, there where no significant differences in synovial cell infiltrates and lymphoid neogenesis according to ACPA status. However, ACPA positive patients had higher levels of T-cells derived and pro-inflammatory cytokines. Given that our ACPA positive and negative patients had no differences in systemic (disease activity) or local (CD68+ cells, SF-IL-6 levels) inflammation, these results suggest different pathogenic mechanisms between these RA subgroups
Disclosure of Interest None Declared
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