title: Changes in Soluble CD18 in Murine Autoimmune Arthritis and Rheumatoid Arthritis Reflect Disease Establishment and Treatment Response.
abstract: BACKGROUND
  In rheumatoid arthritis (RA) immune activation and presence of autoantibodies may precede clinical onset of disease, and joint destruction can progress despite remission. However, the underlying temporal changes of such immune system abnormalities in the inflammatory response during treat-to-target strategies remain poorly understood. We have previously reported low levels of the soluble form of CD18 (sCD18) in plasma from patients with chronic RA and spondyloarthritis. Here, we study the changes of sCD18 before and during treatment of early RA and following arthritis induction in murine models of rheumatoid arthritis.
  
  
  METHODS
  The level of sCD18 was analyzed with a time-resolved immunoflourometric assay in 1) plasma from early treatment naïve RA patients during a treat-to-target strategy (the OPERA cohort), 2) plasma from chronic RA patients, 3) serum from SKG and CIA mice following arthritis induction, and 4) supernatants from synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from 6 RA patients cultured with TNFα or adalimumab.
  
  
  RESULTS
  Plasma levels of sCD18 were decreased in chronic RA patients compared with early RA patients and in early RA patients compared with healthy controls. After 12 months of treatment the levels in early RA patients were similar to healthy controls. This normalization of plasma sCD18 levels was more pronounced in patients with very early disease who achieved an early ACR response. Plasma sCD18 levels were associated with radiographic progression. Correspondingly, the serum level of sCD18 was decreased in SKG mice 6 weeks after arthritis induction compared with healthy littermates. The sCD18 levels in both SKG and CIA mice exhibited a biphasic course after arthritis induction with an initial increase above baseline followed by a decline. Shedding of CD18 from RA SFMC and RA PBMC cultures was increased by TNFα and decreased by adalimumab.
  
  
  CONCLUSIONS
  The plasma sCD18 levels were altered in patients with RA, in mice with autoimmune arthritis and in cell cultures treated with TNFα and adalimumab. Decreased levels of plasma sCD18 could reflect autoimmunity in transition from early to chronic disease and normalization in response to treatment could reflect autoimmunity in remission.
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.|Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors: Tue Wenzel
authors: TW
authors: Kragstrup
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Babak
authors: B
authors: Jalilian
authors: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors: Kresten Krarup
authors: KK
authors: Keller
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Xianwei
authors: X
authors: Zhang
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Julie Kristine
authors: JK
authors: Laustsen
authors: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
authors: Kristian
authors: K
authors: Stengaard-Pedersen
authors: Copenhagen Center for Arthritis Research, Rigshospitalet, Glostrup, Denmark.|Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors: Merete Lund
authors: ML
authors: Hetland
authors: University of Southern Denmark, Odense, Denmark.
authors: Kim
authors: K
authors: Hørslev-Petersen
authors: Odense University Hospital, Odense, Denmark.
authors: Peter
authors: P
authors: Junker
authors: Copenhagen Center for Arthritis Research, Rigshospitalet, Glostrup, Denmark.|Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors: Mikkel
authors: M
authors: Østergaard
authors: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.|Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: Ellen-Margrethe
authors: EM
authors: Hauge
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.|Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: Malene
authors: M
authors: Hvid
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors: Thomas
authors: T
authors: Vorup-Jensen
authors: Department of Biomedicine, Aarhus University, Aarhus, Denmark.|Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.|Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: Bent
authors: B
authors: Deleuran
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D000328:Adult; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D018821:CD18 Antigens / Q000097:blood* / Q000276:immunology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008875:Middle Aged; D013582:Synovial Fluid / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D018821:CD18 Antigens; D000068879:Adalimumab; D008727:Methotrexate