Nature Medicine
1, 448 - 452 (1995)
doi:10.1038/nm0595-448
Positive selection in autoimmunity: Abnormal immune responses to a bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritisSalvatore Albani1, 6, Edward C. Keystone2, J. Lee Nelson3, William E.R. Ollier4, Antonio La Cava1, Ann C. Montemayor1, Deborah A. Weber2, Carlomaurizio Montecucco5, Alberto Martini5
& Dennis A. Carson1
1Departments 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
2Rheumatic Diseases Unit, Wellesley Hospital, 160 Wellesley Street E., Toronto, Ontario M4Y 1J3, Canada
3Immunology & Rheumatology, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, Washington 98104, USA
4ARC Epidemiology Research Unit, University of Manchester, Oxford Road, Manchester M13 9PT, UK
5Department of Pediatrics, University of Pavia, Policlinico S. Matteo, P. le Golgi n. 2, 27100 Pavia, Italy
6Correspondence should be addressed to S.A. 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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