title: Expression of Prostaglandin E2 Enzymes in the Synovium of Arthralgia Patients at Risk of Developing Rheumatoid Arthritis and in Early Arthritis Patients.
abstract: OBJECTIVE
  Arthralgia may precede the development of synovial inflammation in autoantibody-positive individuals at risk of developing rheumatoid arthritis (RA). A major pathway involved in pain is the prostaglandin (PG) E2 pathway. We investigated this pathway in the synovium of individuals with RA-specific autoantibodies and in early arthritis patients.
  
  
  METHODS
  Nineteen autoantibody-positive individuals (IgM-rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) with arthralgia (n=15) and/or a positive family history of RA (n=8), who had been prospectively followed for at least 2 years, were included. In addition, we included early arthritis patients (disease-modifying antirheumatic drug naïve) who after 2 years follow up fulfilled classification criteria for RA (n=63), spondyloarthritis (SpA; n=14), or had unclassified arthritis (UA; n=27). In all subjects we assessed pain and performed synovial biopsy sampling by mini-arthroscopy at baseline. Tissue sections were examined by immunohistochemistry to detect and quantify PGE2 pathway enzymes expression levels (mPGES-1; COX-1 and -2; 15-PGDH).
  
  
  RESULTS
  In both study groups synovial expression of PGE2 enzymes was not clearly related to pain sensation. Expression levels at baseline were not associated with the development of arthritis after follow up (6 out of 19 autoantibody-positive individuals). However, in early SpA patients the expression levels of mPGES-1 and COX-1 were significantly increased compared to RA and UA patients.
  
  
  CONCLUSIONS
  Pain in autoantibody-positive individuals without synovial inflammation who are at risk of developing RA and in early arthritis patients may be regulated by pathways other than the PGE2 pathway or originate at sites other than the synovium. In contrast, in SpA, the PGE2 pathway may be inherently linked to the pathophysiology/etiology of the disease.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Maria J H
authors.initials: MJ
authors.lastname: de Hair
authors.affiliation: Rheumatology research Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Patrick
authors.initials: P
authors.lastname: Leclerc
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Elize C
authors.initials: EC
authors.lastname: Newsum
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Karen I
authors.initials: KI
authors.lastname: Maijer
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Marleen G H
authors.initials: MG
authors.lastname: van de Sande
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands; Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Tamara H
authors.initials: TH
authors.lastname: Ramwadhdoebe
authors.affiliation: Department of Rheumatology, Reade, Amsterdam, The Netherlands.
authors.forename: Dirkjan
authors.initials: D
authors.lastname: van Schaardenburg
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands; Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Lisa G M
authors.initials: LG
authors.lastname: van Baarsen
authors.affiliation: Rheumatology research Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Marina
authors.initials: M
authors.lastname: Korotkova
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Gerlag
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Paul-Peter
authors.initials: PP
authors.lastname: Tak
authors.affiliation: Rheumatology research Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Per-Johan
authors.initials: PJ
authors.lastname: Jakobsson
mesh_terms: D000328:Adult; D018771:Arthralgia / Q000378:metabolism* / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology*; D001323:Autoantibodies / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000378:metabolism; D011446:Prospective Studies; D000071876:Prostaglandin-E Synthases; D012217:Rheumatoid Factor / Q000378:metabolism; D025241:Spondylarthritis / Q000378:metabolism / Q000473:pathology; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology*
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; D012217:Rheumatoid Factor; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone