Synovial Effusion and Synovial Fluid Biomarkers in Psoriatic Arthritis to Assess Intraarticular Tumor Necrosis factor-α Blockade in the Knee Joint

Arthritis Res Ther. 2010;12(4):R148. doi: 10.1186/ar3090. Epub 2010 Jul 19.

Abstract

Introduction: The purpose of this study was the evaluation 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).

Methods: Systemic 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.

Results: At 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).

Conclusions: Synovial 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Psoriatic* / drug therapy
  • Arthritis, Psoriatic* / metabolism
  • Arthritis, Psoriatic* / pathology
  • Biomarkers / metabolism*
  • Drug Monitoring / methods*
  • Drug Monitoring / standards
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Injections, Intra-Articular
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Interleukins / metabolism
  • Knee Joint / metabolism
  • Knee Joint / pathology
  • Leukocyte Count
  • Reproducibility of Results
  • Synovial Fluid / metabolism*
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Biomarkers
  • IL6 protein, human
  • Immunosuppressive Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Interleukin-6
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • interleukin-22