title: Investigation of Complement-activating Pattern Recognition Molecules and Associated Enzymes as Possible Inflammatory Markers in Oligoarticular and Systemic Juvenile Idiopathic Arthritis.
abstract: OBJECTIVE
  The complement system plays a crucial role in the pathogenesis of inflammatory processes. The lectin pathway of the complement system is activated through the recognition of pathogens by soluble pattern recognition molecules (PRM), i.e., mannan-binding lectin (MBL), collectin-LK, and the ficolins. PRM are reportedly correlated to disease activity in rheumatoid arthritis (RA). The aim was to evaluate the pathogenic role of PRM in juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  We measured MBL, M-ficolin, H-ficolin, MBL-associated serine proteases (MASP) 1, MASP-2, MASP-3, and 2 alternative splice products, MBL-associated protein (MAp) 44 and MAp19, in plasma and synovial fluid (SF) of children with persistent oligoarticular (n = 109 in plasma, n = 38 in SF) and systemic JIA (n = 19 in plasma, n = 11 in SF). The concentrations of the proteins were measured by in-house time-resolved immunofluorometric assays.
  
  
  RESULTS
  We observed significantly higher levels of M-ficolin, MASP-1, MASP-2, and MASP-3 in plasma and SF from patients with systemic JIA compared with persistent oligoarticular JIA (p < 0.001). In paired samples of plasma and SF from 47 patients with oligoarticular and systemic JIA, we observed higher concentrations in plasma for both subtypes for 7 of the measured proteins while the reverse relationship was observed for MASP-3. M-ficolin and MASP-2 correlated to erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and platelet count (p < 0.001). M-ficolin was in addition related to the number of active joints and inversely related to hemoglobin levels.
  
  
  CONCLUSIONS
  Our results point to plasma M-ficolin and MASP-2 as inflammatory markers in JIA. The levels of all proteins are higher in plasma than in SF, except for MASP-3, indicating that MASP-3 may be produced locally in joints.
authors.affiliation: From the Department of Pediatrics and Department of Biomedicine, Aarhus University Hospital, Aarhus, Denmark.C. Petri, MD, Department of Pediatrics and Department of Biomedicine, Aarhus University Hospital; S. Thiel, MD, DMSc; J.C. Jensenius, MD, DMSc, Department of Biomedicine, Aarhus University Hospital; T. Herlin, MD, DMSc, Department of Pediatrics, Aarhus University Hospital.
authors.forename: Christine
authors.initials: C
authors.lastname: Petri
authors.affiliation: From the Department of Pediatrics and Department of Biomedicine, Aarhus University Hospital, Aarhus, Denmark.C. Petri, MD, Department of Pediatrics and Department of Biomedicine, Aarhus University Hospital; S. Thiel, MD, DMSc; J.C. Jensenius, MD, DMSc, Department of Biomedicine, Aarhus University Hospital; T. Herlin, MD, DMSc, Department of Pediatrics, Aarhus University Hospital.
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.affiliation: From the Department of Pediatrics and Department of Biomedicine, Aarhus University Hospital, Aarhus, Denmark.C. Petri, MD, Department of Pediatrics and Department of Biomedicine, Aarhus University Hospital; S. Thiel, MD, DMSc; J.C. Jensenius, MD, DMSc, Department of Biomedicine, Aarhus University Hospital; T. Herlin, MD, DMSc, Department of Pediatrics, Aarhus University Hospital.
authors.forename: Jens Christian
authors.initials: JC
authors.lastname: Jensenius
authors.affiliation: From the Department of Pediatrics and Department of Biomedicine, Aarhus University Hospital, Aarhus, Denmark.C. Petri, MD, Department of Pediatrics and Department of Biomedicine, Aarhus University Hospital; S. Thiel, MD, DMSc; J.C. Jensenius, MD, DMSc, Department of Biomedicine, Aarhus University Hospital; T. Herlin, MD, DMSc, Department of Pediatrics, Aarhus University Hospital. troeherl@rm.dk.
authors.forename: Troels
authors.initials: T
authors.lastname: Herlin
mesh_terms: D001171:Arthritis, Juvenile / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers; D002097:C-Reactive Protein; D002648:Child; D002675:Child, Preschool; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D037102:Lectins / Q000097:blood / Q000378:metabolism*; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000378:metabolism*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism*; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism*; D000097604:Ficolins
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D006023:Glycoproteins; D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins; C109662:FCN3 protein, human
keywords: BIOMARKER; COMPLEMENT; FICOLIN; JUVENILE IDIOPATHIC ARTHRITIS; LECTIN