SAT0048 Sinovial fluid cytokines rather than synovial inflammatory cell infiltrates may differentiate rheumatoid arthritis according to the ACPA status:
Authors: J.A. Gόmez-Puerta, R. Celis, M.V. Hernandez, V. Ruiz-Esquide, J. Ramirez, J.D. Cañete, R. Sanmartí
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> 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. <h3>Objectives</h3> 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. <h3>Methods</h3> A cross-sectional study in a single center was done and included 300 consecutive RA patients. We defined a patient as <i>ACPA negative</i> 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). <h3>Results</h3> 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. <h3>Conclusions</h3> 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 <h3>Disclosure of Interest</h3> None Declared