Oral administration of HSP-containing E.Coli extract OM-89 has suppressive effects in autoimmunity. Regulation of autoimmune processes by modulating peripheral immunity towards hsp’s? |
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Authors: | U Wendling J C Farine |
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Institution: | (1) Institute for Infectious Diseases and Immunology, Utrecht University, Yalelaan 1, Utrecht, The Netherlands;(2) Laboratoires OM, 22, rue du Bois-du-Lan, 1217 Meyrin 2, Geneva, Switzerland |
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Abstract: | OM-89 (Subreum) is anE. coli extract used for oral administration in the treatment of rheumatoid arthritis. It contains bacterial heat shock proteins,
namely hsp60 and hsp70, which were shown to be major immunogenic constitutents of the drug. Immunity to bacterial heat-shock
antigens was shown to be a means of immunomodulation of (experimental) autoimmune disease and possibly inflammation in general.
This was demonstrated for mycobacterial hsp60 respectively hsp70 in autoimmune disease models for arthritis, diabetes and
encephalitis. Parallel to the effects displayed by immunisation with hsp, oral administration of hsp-containing OM-89 was
found to modify autoimmune disease in a number of animal models, such as for arthritis, diabetes and SLE. In rats immunisation
with OM-89 was found to lead to proliferative T cell responses to hsp60 and hsp70 of bothE. coli and mycobacterial origin. Conversely, immunisation with hsp antigens could induce T cell reactivity specific for OM-89. Given
this and the autoimmune disease modulating properties of both hsp and OM-89 it is argued that OM-89 acts via the same mechanism
as proposed for hsp: that peripheral tolerance is induced at the level of regulatory T cells with specificity for heat-shock
proteins. This may constitute one mode of action for OM-89 as an arthritis suppressive oral drug in man. |
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Keywords: | E coli autoimmunity hsp’ s arthritis |
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