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 di sease. Using Western blotting and tandem mass spectroscopy, we have identif ied the endoplasmic reticulum chaperone BiP, a 78-kDa glucose-regulated pro tein, as a possible autoantigen, It preferentially stimulated increased pro liferation 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 develop ment of arthritis when given i.v. 1 wk before the injection of type II coll agen arthritis. Preimmunization with BiP suppressed the development of adju vant 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 experime ntal arthritis and that can also prevent the induction of experimental arth ritis. These findings may stimulate the development of new immunotherapies for the treatment of RA.