Fibrocytes in early and long-standing rheumatoid arthritis: a 6-month trial with repeated synovial biopsy, imaging and lung function test

Abstract

ObjectivesTo correlate the level of fibrocytes in peripheral blood, synovial tissue and in vitro culture in rheumatoid arthritis (RA) with changes in disease activity, imaging and pulmonary function.MethodsTwenty patients with early RA (ERA) and 20 patients with long-standing RA (LRA) were enrolled in a 6-month prospective study. Sixteen patients undergoing wrist arthroscopy were healthy controls. Patients with RA underwent pulmonary function tests, ultrasound and synovial ultrasound-guided needle biopsy of the same wrist at baseline and 6 months. Wrist MRI was performed at baseline (all) and 6 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.ResultsFibrocytes were primarily located around vessels and in the subintimal area in the synovium. Fibrocyte levels did not decline during the trial despite effective RA treatment. In the ERA group, increased synovitis assessed by ultrasound was moderate and strongly correlated with an increase in circulating and synovial fibrocyte levels, respectively. Increased synovitis assessed by MRI during the trial in the ERA group was moderately correlated with both increased numbers of circulating and cultured fibrocytes. Absolute diffusion capacity level was overall weakly negatively correlated with the level of circulating and synovial fibrocytes. The decline in diffusion capacity during the trial was moderately correlated with increased levels of synovial fibrocytes.ConclusionOur findings suggest that fibrocytes are involved in RA pathogenesis, both in the synovium and the reduction in lung function seen in a part of patients with RA.Trial registration numberNCT02652299.

Fibrocyte Phenotype of ENTPD1+CD55+ Cells and Its Association with Pain in Osteoarthritic Synovium

“…The significant presence of circulating and synovial fibrocytes in early and late RA, compared to healthy controls, has been well established in a previous study [16]. Moreover, disease activity in the biopsied joint, as assessed by ultrasound, further highlights the potential involvement of fibrocytes in the inflammatory processes associated with RA [28]. Interestingly, while fibrocytes have been extensively studied in the context of RA, our study marks a pioneering effort in investigating their contribution to OA pathology.…”

Targeting fibrocytes in autoimmunity

“…An accumulation of recent data has implicated the fibrocyte, a fibroblast precursor derived from the bone marrow and distinguished by the expression of CD34, CD45, and collagen I, in the pathogenesis of Graves’ ophthalmopathy ( 8 – 10 ). Arising from bone marrow precursors, fibrocytes circulate in elevated levels in different inflammatory and fibrosing disorders, including myelofibrosis, systemic sclerosis, rheumatoid arthritis, and interstitial lung disease ( 11 – 16 ). Fibrocytes are present within the orbital tissues of Graves’ disease patients and their blood levels are increased fivefold, with those having the most severe orbital disease also exhibiting the highest circulating concentrations ( 8 , 17 ).…”