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 pro...
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| Veröffentlicht in: | The Journal of immunology (1950) 2001-02, Vol.166 (3), p.1492-1498 |
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| creator | Corrigall, Valerie M Bodman-Smith, Mark D Fife, Mark S Canas, Benito Myers, Linda K Wooley, Paul H Soh, Cecilia Staines, Norman A Pappin, Darryl J. C Berlo, Suzanne E van Eden, Willem van der Zee, Ruurd Lanchbury, Jerry S Panayi, Gabriel S |
| description | 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. |
| doi_str_mv | 10.4049/jimmunol.166.3.1492 |
| format | Article |
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C ; Berlo, Suzanne E ; van Eden, Willem ; van der Zee, Ruurd ; Lanchbury, Jerry S ; Panayi, Gabriel S</creator><creatorcontrib>Corrigall, Valerie M ; Bodman-Smith, Mark D ; Fife, Mark S ; Canas, Benito ; Myers, Linda K ; Wooley, Paul H ; Soh, Cecilia ; Staines, Norman A ; Pappin, Darryl J. C ; Berlo, Suzanne E ; van Eden, Willem ; van der Zee, Ruurd ; Lanchbury, Jerry S ; Panayi, Gabriel S</creatorcontrib><description>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.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.166.3.1492</identifier><identifier>PMID: 11160188</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Adult ; Animals ; Arthritis, Experimental - etiology ; Arthritis, Experimental - immunology ; Arthritis, Experimental - prevention & control ; Arthritis, Rheumatoid - immunology ; Arthritis, Rheumatoid - pathology ; Autoantibodies - biosynthesis ; Autoantibodies - blood ; Autoantigens - blood ; Autoantigens - immunology ; Autoantigens - isolation & purification ; BiP protein ; Carrier Proteins - administration & dosage ; Carrier Proteins - 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 ; Molecular Chaperones - immunology ; Rats ; Rats, Inbred Lew ; Rats, Wistar ; Synovial Membrane - immunology ; Synovial Membrane - pathology ; T-Lymphocytes - immunology ; T-Lymphocytes - pathology ; Tumor Cells, Cultured</subject><ispartof>The Journal of immunology (1950), 2001-02, Vol.166 (3), p.1492-1498</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-23ffda3c5a035529a1bcc224cb83760486df52ad9419892e21a09a79dec6bc8d3</citedby><cites>FETCH-LOGICAL-c475t-23ffda3c5a035529a1bcc224cb83760486df52ad9419892e21a09a79dec6bc8d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11160188$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Corrigall, Valerie M</creatorcontrib><creatorcontrib>Bodman-Smith, Mark D</creatorcontrib><creatorcontrib>Fife, Mark S</creatorcontrib><creatorcontrib>Canas, Benito</creatorcontrib><creatorcontrib>Myers, Linda K</creatorcontrib><creatorcontrib>Wooley, Paul H</creatorcontrib><creatorcontrib>Soh, Cecilia</creatorcontrib><creatorcontrib>Staines, Norman A</creatorcontrib><creatorcontrib>Pappin, Darryl J. C</creatorcontrib><creatorcontrib>Berlo, Suzanne E</creatorcontrib><creatorcontrib>van Eden, Willem</creatorcontrib><creatorcontrib>van der Zee, Ruurd</creatorcontrib><creatorcontrib>Lanchbury, Jerry S</creatorcontrib><creatorcontrib>Panayi, Gabriel S</creatorcontrib><title>The Human Endoplasmic Reticulum Molecular Chaperone BiP Is an Autoantigen for Rheumatoid Arthritis and Prevents the Induction of Experimental Arthritis</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>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.</description><subject>Adult</subject><subject>Animals</subject><subject>Arthritis, Experimental - etiology</subject><subject>Arthritis, Experimental - immunology</subject><subject>Arthritis, Experimental - prevention & control</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Arthritis, Rheumatoid - pathology</subject><subject>Autoantibodies - biosynthesis</subject><subject>Autoantibodies - blood</subject><subject>Autoantigens - blood</subject><subject>Autoantigens - immunology</subject><subject>Autoantigens - isolation & purification</subject><subject>BiP protein</subject><subject>Carrier Proteins - administration & dosage</subject><subject>Carrier Proteins - immunology</subject><subject>Endoplasmic Reticulum - immunology</subject><subject>Female</subject><subject>Heat-Shock Proteins</subject><subject>Humans</subject><subject>Immunization Schedule</subject><subject>Injections, Intradermal</subject><subject>Injections, Intravenous</subject><subject>Lymphocyte Activation</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred DBA</subject><subject>Mice, Transgenic</subject><subject>Middle Aged</subject><subject>Molecular Chaperones - administration & dosage</subject><subject>Molecular Chaperones - immunology</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Rats, Wistar</subject><subject>Synovial Membrane - immunology</subject><subject>Synovial Membrane - pathology</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - pathology</subject><subject>Tumor Cells, Cultured</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctuEzEUhi0EoqHwBEjIK1hN8GXGnlmGKNBIRVRVWVuO7em48tjBlwaehNfFUYLKjpWP5O__jo5-AN5itGxRO3x8sPNcfHBLzNiSLnE7kGdggbsONYwh9hwsECKkwZzxC_AqpQeEEEOkfQkuMMYM4b5fgN93k4FXZZYebrwOeyfTbBW8Ndmq4soMvwZn6iQjXE9yb2LwBn6yN3CbYM2sSg7SZ3tvPBxDhLeTqa4crIarmKdosz1yGt5E82h8TjDXfVuvi8o2eBhGuPlZrXaun9I9hV6DF6N0ybw5v5fg--fN3fqquf72ZbteXTeq5V1uCB1HLanqJKJdRwaJd0oR0qpdTzlDbc_02BGphxYP_UAMwRINkg_aKLZTvaaX4P3Ju4_hRzEpi9kmZZyT3oSSBEeMEsTpf0HMe4wp5RWkJ1DFkFI0o9jX82T8JTASx-LE3-JELU5QcSyupt6d9WU3G_2UOTdVgQ8nYLL308FGI9Isnas4FofD4R_VH3oIps0</recordid><startdate>20010201</startdate><enddate>20010201</enddate><creator>Corrigall, Valerie M</creator><creator>Bodman-Smith, Mark D</creator><creator>Fife, Mark S</creator><creator>Canas, Benito</creator><creator>Myers, Linda K</creator><creator>Wooley, Paul H</creator><creator>Soh, Cecilia</creator><creator>Staines, Norman A</creator><creator>Pappin, Darryl J. 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C</au><au>Berlo, Suzanne E</au><au>van Eden, Willem</au><au>van der Zee, Ruurd</au><au>Lanchbury, Jerry S</au><au>Panayi, Gabriel S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Human Endoplasmic Reticulum Molecular Chaperone BiP Is an Autoantigen for Rheumatoid Arthritis and Prevents the Induction of Experimental Arthritis</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2001-02-01</date><risdate>2001</risdate><volume>166</volume><issue>3</issue><spage>1492</spage><epage>1498</epage><pages>1492-1498</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><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.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>11160188</pmid><doi>10.4049/jimmunol.166.3.1492</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of immunology (1950), 2001-02, Vol.166 (3), p.1492-1498 |
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| subjects | Adult Animals Arthritis, Experimental - etiology Arthritis, Experimental - immunology Arthritis, Experimental - prevention & control Arthritis, Rheumatoid - immunology Arthritis, Rheumatoid - pathology Autoantibodies - biosynthesis Autoantibodies - blood Autoantigens - blood Autoantigens - immunology Autoantigens - isolation & purification BiP protein Carrier Proteins - administration & dosage Carrier Proteins - 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 Molecular Chaperones - immunology Rats Rats, Inbred Lew Rats, Wistar Synovial Membrane - immunology Synovial Membrane - pathology T-Lymphocytes - immunology T-Lymphocytes - pathology Tumor Cells, Cultured |
| title | The Human Endoplasmic Reticulum Molecular Chaperone BiP Is an Autoantigen for Rheumatoid Arthritis and Prevents the Induction of Experimental Arthritis |
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