The DNA mismatch repair enzyme PMS1 is a myositis‐specific autoantigen
Objective The specificity of the autoantibody response in different autoimmune diseases makes autoantibodies useful for diagnostic purposes. It also focuses attention on tissue‐ and event‐specific circumstances that may select unique molecules for an autoimmune response in specific diseases. Definin...
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| Veröffentlicht in: | Arthritis and rheumatism 2001-02, Vol.44 (2), p.389-396 |
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| creator | Casciola‐Rosen, Livia A. Pluta, Ann F. Plotz, Paul H. Cox, Amy E. Morris, Steven Wigley, Fredrick M. Petri, Michelle Gelber, Allan C. Rosen, Antony |
| description | Objective
The specificity of the autoantibody response in different autoimmune diseases makes autoantibodies useful for diagnostic purposes. It also focuses attention on tissue‐ and event‐specific circumstances that may select unique molecules for an autoimmune response in specific diseases. Defining additional phenotype‐specific autoantibodies may identify such circumstances. This study was undertaken to investigate the disease specificity of PMS1, an autoantigen previously identified in some sera from patients with myositis.
Methods
We used immunoprecipitation analysis to determine the frequency of autoantibodies to PMS1 in sera from patients with myositis, systemic lupus erythematosus, or scleroderma and from healthy controls. Additional antigens recognized by PMS1‐positive sera were further characterized in terms of their susceptibility to cleavage by apoptotic proteases.
Results
PMS1, a DNA mismatch repair enzyme, was identified as a myositis‐specific autoantigen. Autoantibodies to PMS1 were found in 4 of 53 patients with autoimmune myositis (7.5%), but in no sera from 94 patients with other systemic autoimmune diseases (P = 0.016). Additional mismatch repair enzymes (PMS2, MLH1) were targeted, apparently independently. Sera recognizing PMS1 also recognized several other proteins involved in DNA repair and remodeling, including poly(ADP‐ribose) polymerase, DNA‐dependent protein kinase, and Mi‐2. All of these autoantigens were efficiently cleaved by granzyme B, generating unique fragments not observed during other forms of cell death.
Conclusion
PMS1 autoantibodies are myositis specific. The striking correlation between an immune response to a group of granzyme B substrates (functioning in DNA repair and remodeling) and the myositis phenotype strongly implies that tissue‐ and event‐specific biochemical events play a role in selecting these molecules for an autoimmune response. Understanding the role of granzyme B cleavage in this response is an important priority. |
| doi_str_mv | 10.1002/1529-0131(200102)44:2<389::AID-ANR58>3.0.CO;2-R |
| format | Article |
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The specificity of the autoantibody response in different autoimmune diseases makes autoantibodies useful for diagnostic purposes. It also focuses attention on tissue‐ and event‐specific circumstances that may select unique molecules for an autoimmune response in specific diseases. Defining additional phenotype‐specific autoantibodies may identify such circumstances. This study was undertaken to investigate the disease specificity of PMS1, an autoantigen previously identified in some sera from patients with myositis.
Methods
We used immunoprecipitation analysis to determine the frequency of autoantibodies to PMS1 in sera from patients with myositis, systemic lupus erythematosus, or scleroderma and from healthy controls. Additional antigens recognized by PMS1‐positive sera were further characterized in terms of their susceptibility to cleavage by apoptotic proteases.
Results
PMS1, a DNA mismatch repair enzyme, was identified as a myositis‐specific autoantigen. Autoantibodies to PMS1 were found in 4 of 53 patients with autoimmune myositis (7.5%), but in no sera from 94 patients with other systemic autoimmune diseases (P = 0.016). Additional mismatch repair enzymes (PMS2, MLH1) were targeted, apparently independently. Sera recognizing PMS1 also recognized several other proteins involved in DNA repair and remodeling, including poly(ADP‐ribose) polymerase, DNA‐dependent protein kinase, and Mi‐2. All of these autoantigens were efficiently cleaved by granzyme B, generating unique fragments not observed during other forms of cell death.
Conclusion
PMS1 autoantibodies are myositis specific. The striking correlation between an immune response to a group of granzyme B substrates (functioning in DNA repair and remodeling) and the myositis phenotype strongly implies that tissue‐ and event‐specific biochemical events play a role in selecting these molecules for an autoimmune response. Understanding the role of granzyme B cleavage in this response is an important priority.</description><identifier>ISSN: 0004-3591</identifier><identifier>EISSN: 1529-0131</identifier><identifier>DOI: 10.1002/1529-0131(200102)44:2<389::AID-ANR58>3.0.CO;2-R</identifier><identifier>PMID: 11229471</identifier><identifier>CODEN: ARHEAW</identifier><language>eng</language><publisher>New York: John Wiley & Sons, Inc</publisher><subject>Adult ; Autoantibodies ; Autoantigens - immunology ; Base Pair Mismatch ; Biological and medical sciences ; Carrier Proteins - blood ; Carrier Proteins - chemistry ; Carrier Proteins - immunology ; DNA Repair - immunology ; Epitopes ; Female ; Humans ; Male ; Medical sciences ; Middle Aged ; MutL Proteins ; Myositis - immunology ; Neoplasm Proteins ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><ispartof>Arthritis and rheumatism, 2001-02, Vol.44 (2), p.389-396</ispartof><rights>Copyright © 2001 by the American College of Rheumatology</rights><rights>2001 INIST-CNRS</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c5198-a49c45cbf75d1537fff88eec2e2015392865614a2f515408e01b122e2b946b2f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2F1529-0131%28200102%2944%3A2%3C389%3A%3AAID-ANR58%3E3.0.CO%3B2-R$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2F1529-0131%28200102%2944%3A2%3C389%3A%3AAID-ANR58%3E3.0.CO%3B2-R$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=929024$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11229471$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Casciola‐Rosen, Livia A.</creatorcontrib><creatorcontrib>Pluta, Ann F.</creatorcontrib><creatorcontrib>Plotz, Paul H.</creatorcontrib><creatorcontrib>Cox, Amy E.</creatorcontrib><creatorcontrib>Morris, Steven</creatorcontrib><creatorcontrib>Wigley, Fredrick M.</creatorcontrib><creatorcontrib>Petri, Michelle</creatorcontrib><creatorcontrib>Gelber, Allan C.</creatorcontrib><creatorcontrib>Rosen, Antony</creatorcontrib><title>The DNA mismatch repair enzyme PMS1 is a myositis‐specific autoantigen</title><title>Arthritis and rheumatism</title><addtitle>Arthritis Rheum</addtitle><description>Objective
The specificity of the autoantibody response in different autoimmune diseases makes autoantibodies useful for diagnostic purposes. It also focuses attention on tissue‐ and event‐specific circumstances that may select unique molecules for an autoimmune response in specific diseases. Defining additional phenotype‐specific autoantibodies may identify such circumstances. This study was undertaken to investigate the disease specificity of PMS1, an autoantigen previously identified in some sera from patients with myositis.
Methods
We used immunoprecipitation analysis to determine the frequency of autoantibodies to PMS1 in sera from patients with myositis, systemic lupus erythematosus, or scleroderma and from healthy controls. Additional antigens recognized by PMS1‐positive sera were further characterized in terms of their susceptibility to cleavage by apoptotic proteases.
Results
PMS1, a DNA mismatch repair enzyme, was identified as a myositis‐specific autoantigen. Autoantibodies to PMS1 were found in 4 of 53 patients with autoimmune myositis (7.5%), but in no sera from 94 patients with other systemic autoimmune diseases (P = 0.016). Additional mismatch repair enzymes (PMS2, MLH1) were targeted, apparently independently. Sera recognizing PMS1 also recognized several other proteins involved in DNA repair and remodeling, including poly(ADP‐ribose) polymerase, DNA‐dependent protein kinase, and Mi‐2. All of these autoantigens were efficiently cleaved by granzyme B, generating unique fragments not observed during other forms of cell death.
Conclusion
PMS1 autoantibodies are myositis specific. The striking correlation between an immune response to a group of granzyme B substrates (functioning in DNA repair and remodeling) and the myositis phenotype strongly implies that tissue‐ and event‐specific biochemical events play a role in selecting these molecules for an autoimmune response. Understanding the role of granzyme B cleavage in this response is an important priority.</description><subject>Adult</subject><subject>Autoantibodies</subject><subject>Autoantigens - immunology</subject><subject>Base Pair Mismatch</subject><subject>Biological and medical sciences</subject><subject>Carrier Proteins - blood</subject><subject>Carrier Proteins - chemistry</subject><subject>Carrier Proteins - immunology</subject><subject>DNA Repair - immunology</subject><subject>Epitopes</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>MutL Proteins</subject><subject>Myositis - immunology</subject><subject>Neoplasm Proteins</subject><subject>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><issn>0004-3591</issn><issn>1529-0131</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkMtuEzEUhi1ERUPhFZAlJASLCce3mXGKkKKU0kqlgVDWlsc9pkZzCeOJUFjxCH3GPgkOE5UNG1bWOfrO718fIQWDKQPgr5niOgMm2EsOwIC_knLG34hSz2bz85NsfrlS5Vsxheliecyz1QMyub94SCYAIDOhNDskj2P8lkYulHhEDhnjXMuCTcjZ1Q3Sk8s5bUJs7OBuaI9rG3qK7c9tg_Tjh8-MhkgtbbZdDEOId79u4xpd8MFRuxk62w7hK7ZPyIG3dcSn-_eIfDl9d7U4yy6W788X84vMKabLzErtpHKVL9Q1U6Lw3pclouPIIc2al7nKmbTcK6YklAisSmWRV1rmFffiiLwYc9d9932DcTCpucO6ti12m2gKyIUWuUrgcgRd38XYozfrPjS23xoGZifX7FSZnSozyjVSGm6SXGOSXPNHrhEGzGKZ9quU-Gz_9aZq8Ppv3t5mAp7vARudrX1vWxfiPae5Bi4T9WmkfoQat__R6l-lxoX4DTqYnPo</recordid><startdate>200102</startdate><enddate>200102</enddate><creator>Casciola‐Rosen, Livia A.</creator><creator>Pluta, Ann F.</creator><creator>Plotz, Paul H.</creator><creator>Cox, Amy E.</creator><creator>Morris, Steven</creator><creator>Wigley, Fredrick M.</creator><creator>Petri, Michelle</creator><creator>Gelber, Allan C.</creator><creator>Rosen, Antony</creator><general>John Wiley & Sons, Inc</general><general>Wiley</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200102</creationdate><title>The DNA mismatch repair enzyme PMS1 is a myositis‐specific autoantigen</title><author>Casciola‐Rosen, Livia A. ; Pluta, Ann F. ; Plotz, Paul H. ; Cox, Amy E. ; Morris, Steven ; Wigley, Fredrick M. ; Petri, Michelle ; Gelber, Allan C. ; Rosen, Antony</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5198-a49c45cbf75d1537fff88eec2e2015392865614a2f515408e01b122e2b946b2f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adult</topic><topic>Autoantibodies</topic><topic>Autoantigens - immunology</topic><topic>Base Pair Mismatch</topic><topic>Biological and medical sciences</topic><topic>Carrier Proteins - blood</topic><topic>Carrier Proteins - chemistry</topic><topic>Carrier Proteins - immunology</topic><topic>DNA Repair - immunology</topic><topic>Epitopes</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>MutL Proteins</topic><topic>Myositis - immunology</topic><topic>Neoplasm Proteins</topic><topic>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</topic><toplevel>online_resources</toplevel><creatorcontrib>Casciola‐Rosen, Livia A.</creatorcontrib><creatorcontrib>Pluta, Ann F.</creatorcontrib><creatorcontrib>Plotz, Paul H.</creatorcontrib><creatorcontrib>Cox, Amy E.</creatorcontrib><creatorcontrib>Morris, Steven</creatorcontrib><creatorcontrib>Wigley, Fredrick M.</creatorcontrib><creatorcontrib>Petri, Michelle</creatorcontrib><creatorcontrib>Gelber, Allan C.</creatorcontrib><creatorcontrib>Rosen, Antony</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Arthritis and rheumatism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Casciola‐Rosen, Livia A.</au><au>Pluta, Ann F.</au><au>Plotz, Paul H.</au><au>Cox, Amy E.</au><au>Morris, Steven</au><au>Wigley, Fredrick M.</au><au>Petri, Michelle</au><au>Gelber, Allan C.</au><au>Rosen, Antony</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The DNA mismatch repair enzyme PMS1 is a myositis‐specific autoantigen</atitle><jtitle>Arthritis and rheumatism</jtitle><addtitle>Arthritis Rheum</addtitle><date>2001-02</date><risdate>2001</risdate><volume>44</volume><issue>2</issue><spage>389</spage><epage>396</epage><pages>389-396</pages><issn>0004-3591</issn><eissn>1529-0131</eissn><coden>ARHEAW</coden><abstract>Objective
The specificity of the autoantibody response in different autoimmune diseases makes autoantibodies useful for diagnostic purposes. It also focuses attention on tissue‐ and event‐specific circumstances that may select unique molecules for an autoimmune response in specific diseases. Defining additional phenotype‐specific autoantibodies may identify such circumstances. This study was undertaken to investigate the disease specificity of PMS1, an autoantigen previously identified in some sera from patients with myositis.
Methods
We used immunoprecipitation analysis to determine the frequency of autoantibodies to PMS1 in sera from patients with myositis, systemic lupus erythematosus, or scleroderma and from healthy controls. Additional antigens recognized by PMS1‐positive sera were further characterized in terms of their susceptibility to cleavage by apoptotic proteases.
Results
PMS1, a DNA mismatch repair enzyme, was identified as a myositis‐specific autoantigen. Autoantibodies to PMS1 were found in 4 of 53 patients with autoimmune myositis (7.5%), but in no sera from 94 patients with other systemic autoimmune diseases (P = 0.016). Additional mismatch repair enzymes (PMS2, MLH1) were targeted, apparently independently. Sera recognizing PMS1 also recognized several other proteins involved in DNA repair and remodeling, including poly(ADP‐ribose) polymerase, DNA‐dependent protein kinase, and Mi‐2. All of these autoantigens were efficiently cleaved by granzyme B, generating unique fragments not observed during other forms of cell death.
Conclusion
PMS1 autoantibodies are myositis specific. The striking correlation between an immune response to a group of granzyme B substrates (functioning in DNA repair and remodeling) and the myositis phenotype strongly implies that tissue‐ and event‐specific biochemical events play a role in selecting these molecules for an autoimmune response. Understanding the role of granzyme B cleavage in this response is an important priority.</abstract><cop>New York</cop><pub>John Wiley & Sons, Inc</pub><pmid>11229471</pmid><doi>10.1002/1529-0131(200102)44:2<389::AID-ANR58>3.0.CO;2-R</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Autoantibodies Autoantigens - immunology Base Pair Mismatch Biological and medical sciences Carrier Proteins - blood Carrier Proteins - chemistry Carrier Proteins - immunology DNA Repair - immunology Epitopes Female Humans Male Medical sciences Middle Aged MutL Proteins Myositis - immunology Neoplasm Proteins Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis |
| title | The DNA mismatch repair enzyme PMS1 is a myositis‐specific autoantigen |
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