The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis.
Rheumatoid arthritis (RA) is the most common, crippling human autoimmune disease. Using Western blotting and tandem mass spectroscopy, we have identified the endoplasmic reticulum chaperone BiP, a 78-kDa glucose-regulated protein, as a possible autoantigen. It preferentially stimulated increased proliferation of synovial T cells from patients with RA but not from patients with other arthritides. Mice with established collagen- or pristane-induced arthritis developed IgG Abs to BiP. Although BiP injected in CFA failed to induce arthritis in several strains of rats and mice, including HLA-DR4(+/-)- and HLA-DR1(+/+)-transgenic animals, it completely inhibited the development of arthritis when given i.v. 1 wk before the injection of type II collagen arthritis. Preimmunization with BiP suppressed the development of adjuvant arthritis in Lewis rats in a similar manner. This is the first report of a mammalian chaperone that is an autoantigen in human RA and in experimental arthritis and that can also prevent the induction of experimental arthritis. These findings may stimulate the development of new immunotherapies for the treatment of RA.
Corrigall
V M
VM
Department of Rheumatology, Guy's, King's and St. Thomas School of Medicine, King's College London, Guy's Hospital, London, United Kingdom.
Bodman-Smith
M D
MD
Fife
M S
MS
Canas
B
B
Myers
L K
LK
Wooley
P
P
Soh
C
C
Staines
N A
NA
Pappin
D J
DJ
Berlo
S E
SE
van Eden
W
W
van Der Zee
R
R
Lanchbury
J S
JS
Panayi
G S
GS
D000328:Adult; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D001324:Autoantigens / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D002352:Carrier Proteins / Q000008:administration & dosage* / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000276:immunology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins; D006801:Humans; D007115:Immunization Schedule; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008875:Middle Aged; D018832:Molecular Chaperones / Q000008:administration & dosage* / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured
D001323:Autoantibodies; D001324:Autoantigens; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones