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 examined antibody titers against human CCT and other Hsp60 family members in the sera of patients with rheumatic autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematodes, Sjögren syndrome, and mixed connective tissue disease. Autoantibody titers against not only human mitochondrial Hsp60 but also CCT were significantly higher in the sera of patients with rheumatic autoimmune diseases than in healthy control sera. Although immunoglobulin G (IgG) titers against Escherichia coli GroEL were high in all the groups of sera tested, no significant differences in anti-GroEL responses were detected between patients and healthy controls. IgG titers against mycobacterial Hsp65 showed a similar pattern to titers of autoantibodies recognizing GroEL. Immunoabsorption experiments demonstrated that most of the autoantibodies 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 antibodies specific for GroEL (or mycobacterial Hsp65) in addition to antibodies cross-reactive with CCT and Hsp60. Results from immunoblot analyses, together with weak (15% to 20%) amino acid sequence identities between CCT and the other Hsp60 family members, suggested that CCT-reactive autoantibodies recognize conformational epitopes that are conserved among CCT and other Hsp60 family members.
Yokota
S I
SI
HSP Research Institute, Kyoto, Japan.
Hirata
D
D
Minota
S
S
Higashiyama
T
T
Kurimoto
M
M
Yanagi
H
H
Yura
T
T
Kubota
H
H
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000097:blood*; D018834:Chaperonin 60 / Q000276:immunology*; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000276:immunology*; D003429:Cross Reactions; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000097:blood; D005810:Multigene Family; D012216:Rheumatic Diseases / Q000097:blood*; D012859:Sjogren's Syndrome / Q000097:blood
D001323:Autoantibodies; D018834:Chaperonin 60; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins