Do stress proteins have a regulatory role in autoimmune rheumatoid arthritis?

It has been suggested that molecular mimicry between self-(mammalian)-components, such as self-stress, heat-shock proteins (HspIGO 81 bacterial Hsp65 (Mycobacterium [M.] tuberculosis or M. bovisl might be implicated in the human rheumatoid arthritis IRA) --an autoimmune inflammatory joint disease, which is characterized by infiltration of lymphocytespredominantly of the T lineage in the synovial fluid (SF) & of the T & B lineages in the synovial membrane. The observation that higher frequencies of T-cells, from RA individuals relative to the T-cells from healthy individuals, can recognize the self-stress proteins, & the observation that infections with Mycobacterium (in which a link has been found between inducible Hsps & virulence, & where the induced Hsp can be regarded as a virulence factor) can induce stress responses in the host (thought to generally function in immune surveillance & defense against the bacterial infection) provide a basis for suggesting that the bacterial Hsp65 has a potential involvement in the induction of the human autoimmune RA. On entering the mammalian host, pathogenic bacteria might induce a heat-shock response & activate the oxidative stress of the innate immune system phagocytes -functioning to clear the pathogens. As a balance must ensue to allow the induced Hsps t o be superimposed on the regulatory mechanisms controlling the bacterial adaptability to the host stress, as well as the host survival, the Hsps expressed in response to stress shifts might be coordinating the complex balance. Hsp65 epitopes of many infectious bacteria lMycobacferium inclusive) are evolutionarily conserved & recognized as dominant antigens (Ags) by the mammalian immune system. As the conserved epitopes of the Mycobacferium Hsp65 & the conserved self-Hsp60 epitopes share some 50% sequence similarity, overstimulation by infection might also alter the balance of the immune response to the self-stress proteins & lead to destructive surveillance, t o autoimmunity. In other words, the homology between the conserved epitopes of the bacterial Hsp65 & the self-Hsp60 --that implicares Mycobacterium Hsp65 in manifestations involving potential antigenic mimicry [ l I-fails to extend to immunological tolerance. Different Hsps distinguishable on the basis of the molecular mass, are grouped into families denominated: Hsp60(65); Hsp70175); HspSO, each of which subserves, apparently, different functions. The Hsp60(65) & Hsp70(75) multigene family members function as molecular chaperons assisting protein folding & assembly --by reducing the tendency of aggregation during various cellular processes & as such are required for survival. That the conserved Hsp60165) & Hsp70(75) are expressed ubiquitously in prokaryotes & eukaryotes (from bacteria & yeast to mouse & man), both constitutively (in the absence of any kind of stress) & inducible 111 can make them biologically meaningful mimicry elements.