Presence of hsp65 in bacterial extracts (OM-89): a possible mediator of orally-induced tolerance?

Heat shock proteins (HSP) have been implicated in rodent models of autoimmunity, particularly arthritis, and there is suggestive though inconclusive evidence that they may also play a role in human autoimmune disease. The simplest hypothesis is based on molecular mimicry due to the amino-acid sequence homology between mammalian and microbial HSP. Recently OM-89, an extract of several strains of Escherichia coli, has shown some efficacy in the treatment of rheumatoid arthritis (RA) when taken orally. Using species-specific antibodies, we show here that OM-89 contains the 65 kDa HSP (hsp65), while hsp65 was not detected in another bacterial extract containing other microorganisms, including Staphylococcus aureus (OM-85). We suggest that if the human homologue of hsp65 is a relevant target antigen in the human disease, the efficacy of the preparation could be due to induction of oral tolerance or to switching the Th1 response towards Th2. Alternatively, even if the human hsp65 is not a target molecule in RA joints, OM-89 may evoke bystander suppression of joint inflammation via induction of TGF beta-secreting effector cells. These hypotheses should be tested in further studies.