Autoantibodies against chaperonin CCT in human sera with rheumatic autoimmune diseases: comparison with antibodies against other Hsp60 family proteins

Chaperonin CCT containing t-complex polypeptide 1 is a cytosolic molecular chaperone that assists in the folding of actin, tubulin, and other proteins and is a member of the 60-kDa heat shock protein (Hsp60) family. We examin ed antibody titers against human CCT and other Hsp60 family members in the sera of patients with rheumatic autoimmune diseases, including rheumatoid a rthritis, systemic lupus erythematodes, Sjogren syndrome, and mixed connect ive tissue disease. Autoantibody titers against not only human mitochondria l Hsp60 but also CCT were significantly higher in the sera of patients with rheumatic autoimmune diseases than in healthy control sera. Although immun oglobulin G (IgG) titers against Escherichia coli GroEL were high in all th e groups of sera tested, no significant differences in anti-GroEL responses were detected between patients and healthy controls. IgG titers against my cobacterial Hsp65 showed a similar pattern to titers of autoantibodies reco gnizing GroEL. Immunoabsorption experiments demonstrated that most of the a utoantibodies recognizing CCT were cross-reactive with mitochondrial Hsp60, E coli GroEL, and mycobacterial Hsp65. Although most of the anti-Hsp60 IgG recognized CCT, anti-GroEL (or antimycobacterial Hsp65) IgG contained anti bodies specific for GroEL (or mycobacterial Hsp65) in addition to antibodie s crossreactive with CCT and Hsp60. Results from immunoblot analyses, toget her with weak (15% to 20%) amino acid sequence identities between CCT and t he other Hsp60 family members, suggested that CCT-reactive autoantibodies r ecognize conformational epitopes that are conserved among CCT and other Hsp 60 family members.