Abstract

IntroductionThe purpose of this study was theevaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-α blockers in psoriatic arthritis (PsA).MethodsSystemic and local disease activity indexes (disease activity score (DAS); the Ritchie articular index (mRAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); Thompson articular (THOMP) and joint articular (KJAI)-Index ) and ST samples were assessed at baseline, throughout treatment, and during the follow-up in 14 patients affected with PsA who underwent IA injections (0.5 ml to 12.5 mg) in the knee joint of etanercept (E) or placebo (P) once every two weeks for a 10-week period. Total SF white blood cell (WBC) counts (WBC/μl) and SF cytokine/chemokine (CK/CCK) levels were measured before IA-E at baseline, after IA-E, and as long as there were adequate amounts of SF for knee aspiration (post). Characterization of synovial mononuclear cell infiltration and synovial vessels was carried out in 8 out of 14 knees by staining serial sections of synovial tissue biopsies for CD45, CD3, CD68, CD31 and CD105.ResultsAt baseline, CRP and/or ESR were significantly correlated with SF-CK (interleukin- (IL-)1β, IL-1Ra, IL-6, IL-8) and CCK (CCL3). Post-IA injections, there was a decrease in SE in the knees in which aspiration following IA-E injection was possible as well as a significant reduction in SF WBC/μl and in SF-CK (IL-1β, IL-1Ra, IL-6 and IL-22). Pre- and post-IA-E injections, there were significant correlations between ST markers and SF-CK (IL-1β with CD45; IL-1β and IL-6 with CD31) and between SF-CCK (CCL4 and CCL3 with CD3). At the end of the study, there was a significant reduction in disease activity indexes (CRP, DAS, RAI, THOMP, KJAI) as well as in the ST markers (CD45; CD3).ConclusionsSynovial effusion regression is a reliable indicator of the response to IA TNF-α blockers in PsA patients as it is confirmed by the correlation between SF biomarkers to disease activity and synovial tissue inflammation.

Highlights

  • The purpose of this study was theevaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-a blockers in psoriatic arthritis (PsA)

  • Tumor necrosis factor-alpha (TNF-a) plays an important role in the chronic inflammation found in PsA patients, and its increased expression together with that of other pro-inflammatory cytokines, including interferon-g (IFN-g), interleukin (IL) -12, IL-15, IL-17 and IL-18, and in particular, IL-6 and IL-1b, have been demonstrated in PsA synovium [6,7]

  • Four PsA patients were being treated with parenteral E from the time of screening to the end of the IA treatment period

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Summary

Introduction

The purpose of this study was theevaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-a blockers in psoriatic arthritis (PsA). Tumor necrosis factor-alpha (TNF-a) plays an important role in the chronic inflammation found in PsA patients, and its increased expression together with that of other pro-inflammatory cytokines, including interferon-g (IFN-g), interleukin (IL) -12, IL-15, IL-17 and IL-18, and in particular, IL-6 and IL-1b, have been demonstrated in PsA synovium [6,7]. While the efficacy of TNF-a-blocking agents in reducing disease activity in PsA patients [9,10] has been demonstrated, their actual mechanisms of action are not completely understood [11,12,13]. Recent research has made it possible to identify new genetic factors [14,15] and immunopathological mechanisms common to psoriasis and psoriatic joint inflammation [16,17]

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