SAT0048

SINOVIAL FLUID CYTOKINES RATHER THAN SYNOVIAL INFLAMMATORY CELL INFILTRATES MAY DIFFERENTIATE RHEUMATOID ARTHRITIS ACCORDING TO THE ACPA STATUS

J. A. Gómez-Puerta ^1,*R. Celis ¹M. V. Hernandez ¹V. Ruiz-Esquide ¹J. Ramirez ¹J. D. Cañete ¹R. Sanmartí ¹

¹Arthritis Unit, Department of Rheumatology, Hospital Clinic, Barcelona, Spain

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.

Table. SF cytokines in RA patients ACPA positive and ACPA negative. Values expressed by means (SD) (pg/ml)

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