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Positive selection in autoimmunity: Abnormal immune responses to a bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritis

Nature Medicine volume 1, pages 448–452 (1995)Cite this article

Abstract

A novel ‘multistep molecular mimicry’ mechanism for induction of rheumatoid arthritis (RA) by bacterial antigens that activate T lymphocytes previously ‘educated’ by peptides derived from a class of human histocompatibility antigens is reported here. These antigens have the amino acid sequence QKRAA, which is also present on the Escherichia coli heat-shock protein dnaj. Synovial fluid cells of early RA patients have strong immune responses to the bacterial antigen, but cells from normal subjects or controls with other autoimmune diseases do not. The activated T cells may cross-react with autologous dnaj heat-shock proteins that are expressed at synovial sites of inflammation. Our findings may have direct relevance to new strategies for the immune therapy of RA.

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Authors and Affiliations

  1. Departments of Medicine and Pediatrics, and The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093-0663, USA

    Salvatore Albani, Antonio La Cava, Ann C. Montemayor & Dennis A. Carson

  2. Rheumatic Diseases Unit, Wellesley Hospital, 160 Wellesley Street E., Toronto, Ontario, M4Y 1J3, Canada

    Edward C. Keystone & Deborah A. Weber

  3. Immunology & Rheumatology, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, Washington, 98104, USA

    J. Lee Nelson

  4. ARC Epidemiology Research Unit, University of Manchester, Oxford Road, Manchester, M13 9PT, UK

    William E.R. Ollier

  5. Department of Pediatrics, University of Pavia, Policlinico S. Matteo, P. le Golgi n. 2, 27100, Pavia, Italy

    Carlomaurizio Montecucco & Alberto Martini

Authors
  1. Salvatore Albani
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  2. Edward C. Keystone
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  3. J. Lee Nelson
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  4. William E.R. Ollier
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  5. Antonio La Cava
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  6. Ann C. Montemayor
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  7. Deborah A. Weber
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  8. Carlomaurizio Montecucco
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  9. Alberto Martini
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  10. Dennis A. Carson
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Albani, S., Keystone, E., Nelson, J. et al. Positive selection in autoimmunity: Abnormal immune responses to a bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritis. Nat Med 1, 448–452 (1995). https://doi.org/10.1038/nm0595-448

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