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

ABSTRACT: To 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. Twenty 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. Fibrocytes 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. Our 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. NCT02652299.

SUBMITTER: Just SA

PROVIDER: S-EPMC7938972 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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

Just Søren Andreas SA Nielsen Christian C Werlinrud Jens Christian JC Larsen Pia Veldt PV Hejbøl Eva Kildall EK Tenstad Helene Broch HB Daa Schrøder Henrik H Barington Torben T Torfing Trine T Humby Frances F Lindegaard Hanne H

RMD open 20210301 1

<h4>Objectives</h4>To 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.<h4>Methods</h4>Twenty 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 ultr ...[more]

PMID: 33674419

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Project description:IntroductionStandardised scoring systems for rheumatoid arthritis (RA) joint disease activity include Larsen score for radiographs, rheumatoid arthritis magnetic resonance imaging score (RAMRIS) for MRI and using the European League Against Rheumatisms-Outcome Measures in Rheumatology (EULAR-OMERACT) score for ultrasound (US) images. The aim of this prospective study was to investigate the relationship between histological synovitis and radiological synovitis, assessed by conventional X-ray, US and MRI of the wrist radiocarpal joint.Methods20 patients with treatment naive early RA (ERA) and 20 with long-standing RA (LRA) were enrolled in a 6-month prospective study. Patients with RA underwent US-guided synovial biopsy, X-ray and US of the wrist at enrolment and 6 months. MRI at baseline and also at 6 months for the ERA group, and scored with the RAMRIS system. X-ray was scored by Larsen score and US by the EULAR-OMERACT system. Synovial biopsy inflammation was determined by the Krenn score.ResultsIn the ERA group at baseline, Krenn score was correlated strongly with both US combined score (r = 0.77 p < 0.001) and MRI synovitis score (r = 0.85 p < 0.001), while uncorrelated at 6 months. In the LRA group at baseline, these scores correlated strongly (r = 0.83, p < 0.001) to moderately (r = 0.61, p = 0.002), and persisted at 6 months for US score (r = 0.81 p < 0.001). For all patients with RA, change in Krenn score between baseline and 6 months was correlated with both change in US combined score (r = 0.65, p < 0.001) and change in MRI synovitis score (r = 0.50, p = 0.03).ConclusionThe MRI RAMRIS synovitis score and EULAR-OMERACT US scoring system are sensitive measures of histological synovitis in LRA and ERA. After 6 months, this correlation persists in the established RA group, but not in the ERA group. Overall, decreases in MRI/US synovitis are associated with reductions in histological synovitis. The study validates the use of MRI RAMRIS and EULAR-OMERACT US scores as surrogate markers of histological synovitis in established RA and early untreated RA.

Project description:IntroductionDespite the widespread use of magnetic resonance imaging (MRI) and Doppler ultrasound for the detection of rheumatoid arthritis (RA) disease activity, little is known regarding the association of imaging-detected activity and synovial pathology. The purpose of this study was to compare site-specific release of inflammatory mediators and evaluate the corresponding anatomical sites by examining colour Doppler ultrasound (CDUS) and MRI scans.MethodsRA patients were evaluated on the basis of CDUS and 3-T MRI scans and subsequently underwent synovectomy using a needle arthroscopic procedure of the hand joints. The synovial tissue specimens were incubated for 72 hours, and spontaneous release of monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), macrophage inflammatory protein 1? (MIP-1?) and IL-8 was measured by performing multiplex immunoassays. Bone marrow oedema (BME), synovitis and erosion scores were estimated on the basis of the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Mixed models were used for the statistical analyses. Parsimony was achieved by omitting covariates with P > 0.1 from the statistical model.ResultsTissue samples from 58 synovial sites were obtained from 25 patients. MCP-1 was associated with CDUS activity (P = 0.009, approximate Spearman's ? = 0.41), RAMRIS BME score (P = 0.01, approximate Spearman's ? = 0.42) and RAMRIS erosion score (P = 0.03, approximate Spearman's ? = 0.31). IL-6 was associated with RAMRIS synovitis score (P = 0.04, approximate Spearman's ? = 0.50), BME score (P = 0.04, approximate Spearman's ? = 0.31) and RAMRIS erosion score (P = 0.03, approximate Spearman's ? = 0.35). MIP-1? was associated with CDUS activity (P = 0.02, approximate Spearman's ? = 0.38) and RAMRIS synovitis scores (P = 0.02, approximate Spearman's ? = 0.63). IL-8 associations with imaging outcome measures did not reach statistical significance.ConclusionsThe association between imaging activity and synovial inflammatory mediators underscores the high sensitivity of CDUS and MRI in the evaluation of RA disease activity. The associations found in our present study have different implications for synovial mediator releases and corresponding imaging signs. For example, MCP-1 and IL-6 were associated with both general inflammation and bone destruction, in contrast to MIP-1?, which was involved solely in general synovitis. The lack of association of IL-8 with synovitis was likely underestimated because of a large proportion of samples above assay detection limits among the patients with the highest synovitis scores.

Dataset Information

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

Publications

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

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