POS0377\u2005FIBROCYTES IN EARLY AND LONGSTANDING RHEUMATOID ARTHRITIS: A 6-MONTH TRIAL WITH REPEATED SYNOVIAL BIOPSY, IMAGING, AND LUNG FUNCTION TEST

Abstract

Fibrocytes are bone marrow-derived cells, that express both hematopoietic and stromal markers. In murine collagen-induced arthritis models circulating fibrocytes have been found to home to inflamed joints and enhance arthritis activity. The cell has, therefore, been proposed to be precursor cells for the fibroblast-like synoviocytes (FLS), which are central in the Rheumatoid Arthritis (RA) pathogenesis. Fibrocytes levels are further correlated with disease progression and mortality in interstitial lung disease (ILD) and identified as a new treatment target. ILD is also an extra-articular manifestation of RA (RA-ILD), leading to a reduced lung diffusion capacity and increased mortality.To correlate the level of fibrocytes in peripheral blood, synovial tissue, and in vitro culture in RA to changes in disease activity, imaging, and pulmonary function.Twenty patients with early RA (ERA) and 20 patients with longstanding RA (LRA) were enrolled in a six months prospective study. Sixteen patients undergoing wrist arthroscopy were healthy controls. RA patients underwent pulmonary function tests, ultrasound, and synovial ultrasound-guided needle biopsy of the same wrist, at baseline and six months. Wrist magnetic resonance imaging was performed at baseline (all) and six months (ERA). Circulating fibrocytes were measured by flow cytometry, in vitro by the number of monocytes that were differentiated to fibrocytes, and in synovial biopsies by counting in histological sections.Fibrocyte levels did not decline during the trial despite effective RA treatment. Fibrocytes were primarily located around vessels and in the subintimal area in the synovium (Figure 1A and 1B, fibrocytes marked with arrows). In the ERA group, increased synovitis assessed by ultrasound was moderate and strongly correlated to respectively increase in circulating and synovial fibrocyte levels. Increased synovitis assessed by MRI during the trial in the ERA group, was moderately correlated to both increased numbers of circulating and cultured fibrocytes. Absolute diffusion capacity level was overall weakly negatively correlated to the level of circulating and synovial fibrocytes. The decline in forced ventilatory capacity and diffusion capacity during the trial was moderately correlated to increased levels of synovial fibrocytes (Figure 1C and 1D).Our findings point to fibrocytes as key mediators of RA pathogenesis, and as a possible pathogenic link between the disease process in the synovium and RA lung affection. Studies are needed to investigate if the new therapies targeting fibrocyte differentiation/migration could be a path forward in RA/RA-ILD treatment.None declared