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Ann Rheum Dis 2004;63:ii28-ii31 doi:10.1136/ard.2004.028225
  • Genetics

What precedes development of rheumatoid arthritis?

  1. L Klareskog1,
  2. L Alfredsson2,
  3. S Rantapää-Dahlqvist3,
  4. E Berglin3,
  5. P Stolt2,
  6. L Padyukov1
  1. 1Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden
  2. 2Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  3. 3Department of Rheumatology, Umeå University and University Hospital, Umeå, Sweden
  1. Correspondence to:
    L Klareskog
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital, 171 76 Stockholm, Sweden; Lars.Klareskogmedks.ki.se

    Abstract

    Studies on aetiology of inflammatory diseases such as rheumatoid arthritis (RA) need to investigate the potential environmental triggers that are active before onset of disease, the genetic context in which these triggers act, and whether the presence of such triggers in an arthritis prone genetic context will give rise to the immune reactions associated with/preceding RA. Such knowledge would help not only to address much better the issue of causality of these potential triggers and the immune reactions, but also to carry out various interventions aimed at influencing the disease provoking immune events before development of clinical signs of disease.

    This short report summarises recent data demonstrating (a) the presence of anticitrullin antibodies or rheumatoid factors in between a third and half of patients with RA before development of clinical signs; (b) long term smoking is associated with a high risk of future development of seropositive but not seronegative RA; and (c) a strong gene–environment interaction between smoking and SE genes in the development of seropositive RA.

    We conclude that, in a certain genetic context, smoking is a potential trigger of RA, and a combination of the two factors is associated with the occurrence of immune reactions long before the onset of RA.

    Footnotes

    • The studies from our own laboratory referred to in this report were supported by grants from the Swedish Research Council, the insurance company AFA, King Gustaf Vth 80-year Foundation and the Swedish Association against Rheumatism.

    • During the preparation of this article, LK received support from the Fernström Foundation to spend time as guest scientist at Harvard Medical School (Department of Rheumatology and Department of Neuroscience).

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