There are several aspects of the mycobacteria which lead to the possibility that these organisms, or antigens cross-reactive with them, are involved in autoimmune disease.
1. Tuberculosis is one of a group of diseases in which there is a rise in the percentage of circulating IgG molecules that lack terminal galactose from the oligosaccharide which is always present on the CHZ domain of the Fc. This 'glycoform' of IgG is known as agalactosyl IgG. There is also a transient rise during episodes of erythema nodosum leprosum (ENL) in leprosy. The other conditions where agalactosyl IgG rises strikingly are Crohn's disease, rheumatoid arthritis and rodent models of autoimmune arthritis.
2. The mycobacterial 65 kDa heat shock protein (or autoantigens cross-reactive with it) is implicated in the pathogenesis of the rodent models of arthritis, and of the human disease.
3. Induction of arthritis in the rodent models can be blocked by pretreatment with the mycobacterial 65 kDa hsp.
In view of the fact that mycobacteria are ubiquitous in soil and water, but absent from the commensal microbial flora, there is the tantalizing possibility that variable exposure to mycobacteria in different geographical environments plays a role in the regulation of susceptibility to certain autoimmune diseases.
See also: Autoimmunity; Bacteria, immunity to; Bacterial cell walls; BCG; Delayed-type hypersensitivity; Glycosylation of immune system molecules; Granuloma; Hypersensitivity reactions; Stress proteins; T cell vaccination.
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