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

Abstract

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.

Experimental immunization with anti-rheumatic bacterial extract OM-89 induces T cell responses to heat shock protein (hsp)60 and hsp70; modulation of peripheral immunological tolerance as its possible mode of action in the treatment of rheumatoid arthritis (RA)

“…The presence of bacterial hsp in OM-89 had been suggested previously, on the basis of the reactivity of some selected hsp60-specific antibodies with OM-89 in Western blots [4]. The present findings have given the evidence that the presence of such hsp can be recognized by specific T cells, that they are capable of priming for raised secondary T cell responses, and finally that besides hsp60, also hsp70 is present in OM-89 concentrate.…”

“…The presence of E. coli hsp60 (GroEL) in OM-89 was postulated [3] and shown already by the staining of OM-89 with hsp60-specific MoAbs [4]. Bacterial hsp were shown to have the capacity of preventing experimental arthritis upon prior immunization.…”

Rheumatoid arthritis and enteric bacteria

“…Escherichia coli GroEL stress protein belongs to the hsp60 family, together with the structurally related mycobacterial hsp65 showing cross-reactivity with many bacteria [ 120]. Polla et al [ 130] showed that OM-8980 contained the 65 kDa hsp using species-specific antibodies. OM-8980, a peptidic E. coli extract free of LPS, is a new medication of biological origin with immunomodulating properties [126][127][128][129].…”

Oral insulin for diabetes prevention in NOD mice: potentiation by enhancing Th2 cytokine expression in the gut through bacterial adjuvant

“…Since oral endotoxin treatment may not be devoid of adverse effects, including the induction of autoantibody formation in the peritoneal cavity and lamina propria [19] we selected an LPS-free bacterial preparation as adjuvant. OM-89 is a protein extract of Escherichia coli containing mainly acidic glycoproteins of 10-300 kDa molecular weight and less than 12 ppm LPS [20][21][22]. This compound is presently being used for adjuvant treatment of some infectious diseases and rheumatoid arthritis [20,23].…”