The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis

Corrigall, V. M., Bodman-Smith, M. D., Fife, M. S., Canas, B., Myers, L. K., Wooley, P., Soh, C., Staines, N. A., Pappin, D. J., Berlo, S. E., van Eden, W., van Der Zee, R., Lanchbury, J. S., Panayi, G. S. (February 2001) The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis. J Immunol, 166 (3). pp. 1492-8. ISSN 0022-1767 (Print)0022-1767 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/11160188

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Adult Animals Arthritis, Experimental/etiology/ immunology/ prevention & control Arthritis, Rheumatoid/ immunology/pathology Autoantibodies/biosynthesis/blood Autoantigens/blood/ immunology/isolation & purification Carrier Proteins/ administration & dosage/ immunology Endoplasmic Reticulum/immunology Female Heat-Shock Proteins Humans Immunization Schedule Injections, Intradermal Injections, Intravenous Lymphocyte Activation Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic Middle Aged Molecular Chaperones/ administration & dosage/ immunology Rats Rats, Inbred Lew Rats, Wistar Synovial Membrane/immunology/pathology T-Lymphocytes/immunology/pathology Tumor Cells, Cultured
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organs, tissues, organelles, cell types and functions > organelles, types and functions > endoplasmic reticulum
diseases & disorders > inflammation
biotechnology > chromatography > protein purification
CSHL Authors:
Communities: CSHL labs > Pappin lab
Depositing User: Matt Covey
Date: 1 February 2001
Date Deposited: 22 Jan 2014 20:04
Last Modified: 22 Jan 2014 20:04
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29227

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