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Up regulation of monocyte chemoattractant protein-1 expression in anti-citrulline antibody and immunoglobulin M rheumatoid factor positive subjects precedes onset of inflammatory response and development of overt rheumatoid arthritis
  1. S Rantapää-Dahlqvist1,
  2. K Boman2,
  3. A Tarkowski3,
  4. G Hallmans1
  1. 1Departments of Rheumatology and Nutritional Research, Umeå University, Umeå, Sweden
  2. 2Department of Medicine, Skellefteå Hospital, Skellefteå, Sweden
  3. 3Department of Rheumatology and Inflammation Research, Göteborg University, Göteborg, Sweden
  1. Correspondence to:
    S Rantapää-Dahlqvist
    Department of Rheumatology, University Hospital, SE-901 85 Umeå, Sweden; Solbritt.Rantapaa.Dahlqvist{at}


Objective: To analyse the inflammatory mediators, including monocyte chemoattractant protein-1 (MCP-1), in blood samples donated years before onset of rheumatoid arthritis. Previously, it has been shown in these individuals that antibodies against cyclic citrullinated peptide (anti-CCP) detectable years before the onset of symptoms have a high predictive value for development of rheumatoid arthritis.

Methods: A nested case–control study was performed: patients with rheumatoid arthritis were identified from among blood donors antedating onset by a median of three years (pre-patients, n = 92); four matched controls were selected randomly for each pre-patient. Plasma were analysed for secretory phospholipase A2 (sPLA2) and MCP-1 using ELISA, for high-sensitivity C reactive protein (hsCRP) using the chemiluminescence method and for interleukin-6 using a sensitive bioassay.

Results: When the results were stratified for the presence of anti-CCP antibodies and immunoglobulin M-rheumatoid factor (IgM-RF), only MCP-1 levels were found to be significantly raised in patients with anti-CCP and IgM-RF compared with controls.

Conclusion: Levels of MCP-1 were significantly increased in the plasma of patients having anti-CCP antibodies or IgM-RF and who later developed rheumatoid arthritis. These findings indicate up regulation of chemotactic activity for leucocytes before the development of rheumatoid arthritis.

  • CCP, cyclic citrullinated peptide
  • CRP, C reactive protein
  • hsCRP, high-sensitivity C reactive protein
  • IgM-RF, immunoglobulin M-rheumatoid factor
  • MCP, monocyte chemoattractant protein
  • sPL, secretory phospholipase

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  • Funding: This study was supported by grants from the Swedish Research Council (K2003-74XD-14705-01), King Gustaf V’s 80-Year Fund, the Swedish Rheumatism Association, and the Medical Faculty of Umeå University, Umeå, Sweden.

  • Competing interests: None declared.

  • Published Online First 1 June 2006