title: Synovial effusion and synovial fluid biomarkers in psoriatic arthritis to assess intraarticular tumor necrosis factor-α blockade in the knee joint.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy. ugo.fiocco@unipd.it
authors.forename: Ugo
authors.initials: U
authors.lastname: Fiocco
authors.forename: Paolo
authors.initials: P
authors.lastname: Sfriso
authors.forename: Francesca
authors.initials: F
authors.lastname: Oliviero
authors.forename: Pascale
authors.initials: P
authors.lastname: Roux-Lombard
authors.forename: Elena
authors.initials: E
authors.lastname: Scagliori
authors.forename: Luisella
authors.initials: L
authors.lastname: Cozzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Lunardi
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.forename: Maristella
authors.initials: M
authors.lastname: Vezzù
authors.forename: Serena
authors.initials: S
authors.lastname: Dainese
authors.forename: Beatrice
authors.initials: B
authors.lastname: Molena
authors.forename: Anna
authors.initials: A
authors.lastname: Scanu
authors.forename: Roberto
authors.initials: R
authors.lastname: Nardacchione
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Rubaltelli
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Dayer
authors.forename: Leonardo
authors.initials: L
authors.lastname: Punzi
mesh_terms: D015535:Arthritis, Psoriatic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism*; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count; D015203:Reproducibility of Results; D013582:Synovial Fluid / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D000097043:Interleukin-22
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22; C508600:IL6 protein, human