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On the origins of complex immune-mediated disease: the example of rheumatoid arthritis

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Abstract

This essay discusses strategies for understanding the origins and outcomes of complex chronic inflammatory diseases using genetic and environmental determinants as tools for new definitions of disease subsets. Rheumatoid arthritis has been chosen as the prototype to illustrate these general concepts. Through recent data on two different disease subsets, it has been possible to devise a new molecular model for disease development by incorporating multiple genes and environmental agents which generate immune reactions that may eventually cause disease. These kinds of studies, aiming to integrate genetic epidemiology and molecular immunology, require close proximity between institutions for molecular medicine, clinical departments able to provide follow-up, careful surveillance of large patient groups and collaboration with experts in epidemiology and biostatistics.

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Acknowledgements

The authors are indebted to the research groups at the Centre for Molecular Medicine, to clinicians at the Karolinska University Hospital Rheumatology clinic and to members of the team of the Institute for Environmental Medicine at Karolinska Institutet for discussions leading to the concepts and much of the data referred to in this article. Susanne Karlfeldt provided critical and most valuable assistance in completing the manuscript. Lars Klareskog also wants to acknowledge a stipend from the San Michele Foundation that provided time and environment for the writing of this essay.

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Authors and Affiliations

  1. Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Solna, 171 76, Stockholm, Sweden

    Lars Klareskog

  2. Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Sara Wedrén & Lars Alfredsson

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  1. Lars Klareskog
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  2. Sara Wedrén
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Correspondence to Lars Klareskog.

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Klareskog, L., Wedrén, S. & Alfredsson, L. On the origins of complex immune-mediated disease: the example of rheumatoid arthritis. J Mol Med 87, 357–362 (2009). https://doi.org/10.1007/s00109-008-0437-9

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  • DOI: https://doi.org/10.1007/s00109-008-0437-9

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