AUTOANTIBODIES TO HUMAN HEAT-SHOCK PROTEIN (HSP)60 MAY BE INDUCED BY ESCHERICHIA-COLI GROEL

The 65-kD hsp from Mycobacterium tuberculosis has been reported to ind uce an autopathogenic subset of T cells in at least two animal models of autoimmune disease. Reports of increased expression of human hsp60 in the inflamed synovial tissue of rheumatoid arthritis (RA) patients, increased proliferation of RA synovial fluid T cells to mycobacterial hsp65, and increased levels of anti-mycobacterial hsp65 antibody in s ynovial fluid, have suggested that the highly homologous human (hu) hs p60 may be recognized as an autoantigen in RA patients. In the present study, we have examined by ELISA the serum IgG antibody levels to myc obacterial hsp65 and hu hsp60, as well as to the Escherichia coli hsp6 0, groEL, in patients with RA, systemic lupus erythematosus (SLE), Rei ter's syndrome, active tuberculosis, and normal controls. In all these groups, the levels of anti-groEL and anti-hu hsp60 were significantly higher than the anti-mycobacterial hsp65. Anti-hu hsp60 was positivel y correlated with anti-groEL, but not with anti-mycobacterial hsp65. A nti-hu hsp60 was competitively inhibited by either soluble groEL or hu hsp60, but little or none by mycobacterial hsp65. Reiter's sera were found to have somewhat higher levels of anti-groEL and anti-hu hsp60 t han did normal controls. We conclude that IgG anti-hu hsp60 autoantibo dies arise primarily as a consequence of the humoral immune response t o E. coil groEL through the recognition of cross-reactive epitopes.