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Epitopes of human fibrin recognized by the rheumatoid arthritis‐specific autoantibodies to citrullinated proteins
Formation of the epitopes recognized by the rheumatoid arthritis (RA)‐specific autoantibodies to citrullinated proteins (ACPA) on filaggrin and on the α‐ and β‐chains of fibrin, their synovial target, requires conversion of their arginyl residues into citrullyl residues, but is also affected by thei...
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| Published in: | European journal of immunology 2006-08, Vol.36 (8), p.2250-2263 |
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| cites | cdi_FETCH-LOGICAL-c4500-4c9a822661b1619ed8f94f5007619e718e435d58918d2297e33cb6d7e44536443 |
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| container_issue | 8 |
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| container_title | European journal of immunology |
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| creator | Sebbag, Mireille Moinard, Nathalie Auger, Isabelle Clavel, Cyril Arnaud, Jacques Nogueira, Leonor Roudier, Jean Serre, Guy |
| description | Formation of the epitopes recognized by the rheumatoid arthritis (RA)‐specific autoantibodies to citrullinated proteins (ACPA) on filaggrin and on the α‐ and β‐chains of fibrin, their synovial target, requires conversion of their arginyl residues into citrullyl residues, but is also affected by their amino‐acyl environment. Using competition with five citrullinated filaggrin‐derived peptides bearing major ACPA epitopes, we confirmed the close cross‐reactivity between filaggrin and citrullinated fibrin. To identify the sequential epitopes recognized on fibrin by ACPA, 71 citrullinated 15‐mer peptides derived from all the sites of the α‐ and β‐chains of fibrin harboring arginyl residues were tested by ELISA using ACPA‐positive RA sera exhibiting different reactivity profiles to the five filaggrin peptides. We identified 18 fibrin‐derived peptides bearing ACPA epitopes. Regarding the ability of fibrinogen arginyl residues to be citrullinated in vitro, 11 of the peptides likely correspond to in vivo targeted epitopes. Two out of them bear major epitopes and are located in the central globular domain of the protein. In the synovial tissue, fibrin citrullination and ACPA binding could impair fibrin degradation by plasmin. The immunological conflict between ACPA and fibrin could therefore sustain synovial inflammation not only via pro‐inflammatory effector mechanisms but also via impairment of fibrinolysis. |
| doi_str_mv | 10.1002/eji.200535790 |
| format | article |
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Using competition with five citrullinated filaggrin‐derived peptides bearing major ACPA epitopes, we confirmed the close cross‐reactivity between filaggrin and citrullinated fibrin. To identify the sequential epitopes recognized on fibrin by ACPA, 71 citrullinated 15‐mer peptides derived from all the sites of the α‐ and β‐chains of fibrin harboring arginyl residues were tested by ELISA using ACPA‐positive RA sera exhibiting different reactivity profiles to the five filaggrin peptides. We identified 18 fibrin‐derived peptides bearing ACPA epitopes. Regarding the ability of fibrinogen arginyl residues to be citrullinated in vitro, 11 of the peptides likely correspond to in vivo targeted epitopes. Two out of them bear major epitopes and are located in the central globular domain of the protein. In the synovial tissue, fibrin citrullination and ACPA binding could impair fibrin degradation by plasmin. The immunological conflict between ACPA and fibrin could therefore sustain synovial inflammation not only via pro‐inflammatory effector mechanisms but also via impairment of fibrinolysis.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/eji.200535790</identifier><identifier>PMID: 16838278</identifier><language>eng</language><publisher>Weinheim: WILEY‐VCH Verlag</publisher><subject>Amino Acid Sequence ; Antibody Specificity ; Anti‐citrullinated protein autoantibodies ; Arthritis, Rheumatoid - immunology ; Arthritis, Rheumatoid - metabolism ; Autoantibodies - immunology ; Citrulline ; Citrulline - immunology ; Citrulline - metabolism ; Deimination ; Enzyme-Linked Immunosorbent Assay ; Epitopes - chemistry ; Epitopes - immunology ; Fibrin ; Fibrin - chemistry ; Fibrin - immunology ; Fibrin - metabolism ; Fibrinogen - chemistry ; Fibrinogen - immunology ; Fibrinogen - metabolism ; Humans ; Intermediate Filament Proteins - immunology ; Intermediate Filament Proteins - metabolism ; Life Sciences ; Models, Molecular ; Molecular Sequence Data ; Protein Structure, Quaternary ; Rheumatoid arthritis</subject><ispartof>European journal of immunology, 2006-08, Vol.36 (8), p.2250-2263</ispartof><rights>Copyright © 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4500-4c9a822661b1619ed8f94f5007619e718e435d58918d2297e33cb6d7e44536443</citedby><cites>FETCH-LOGICAL-c4500-4c9a822661b1619ed8f94f5007619e718e435d58918d2297e33cb6d7e44536443</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%2Feji.200535790$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Feji.200535790$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,315,786,790,891,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16838278$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-04171981$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Sebbag, Mireille</creatorcontrib><creatorcontrib>Moinard, Nathalie</creatorcontrib><creatorcontrib>Auger, Isabelle</creatorcontrib><creatorcontrib>Clavel, Cyril</creatorcontrib><creatorcontrib>Arnaud, Jacques</creatorcontrib><creatorcontrib>Nogueira, Leonor</creatorcontrib><creatorcontrib>Roudier, Jean</creatorcontrib><creatorcontrib>Serre, Guy</creatorcontrib><title>Epitopes of human fibrin recognized by the rheumatoid arthritis‐specific autoantibodies to citrullinated proteins</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>Formation of the epitopes recognized by the rheumatoid arthritis (RA)‐specific autoantibodies to citrullinated proteins (ACPA) on filaggrin and on the α‐ and β‐chains of fibrin, their synovial target, requires conversion of their arginyl residues into citrullyl residues, but is also affected by their amino‐acyl environment. Using competition with five citrullinated filaggrin‐derived peptides bearing major ACPA epitopes, we confirmed the close cross‐reactivity between filaggrin and citrullinated fibrin. To identify the sequential epitopes recognized on fibrin by ACPA, 71 citrullinated 15‐mer peptides derived from all the sites of the α‐ and β‐chains of fibrin harboring arginyl residues were tested by ELISA using ACPA‐positive RA sera exhibiting different reactivity profiles to the five filaggrin peptides. We identified 18 fibrin‐derived peptides bearing ACPA epitopes. Regarding the ability of fibrinogen arginyl residues to be citrullinated in vitro, 11 of the peptides likely correspond to in vivo targeted epitopes. Two out of them bear major epitopes and are located in the central globular domain of the protein. In the synovial tissue, fibrin citrullination and ACPA binding could impair fibrin degradation by plasmin. The immunological conflict between ACPA and fibrin could therefore sustain synovial inflammation not only via pro‐inflammatory effector mechanisms but also via impairment of fibrinolysis.</description><subject>Amino Acid Sequence</subject><subject>Antibody Specificity</subject><subject>Anti‐citrullinated protein autoantibodies</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Autoantibodies - immunology</subject><subject>Citrulline</subject><subject>Citrulline - immunology</subject><subject>Citrulline - metabolism</subject><subject>Deimination</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epitopes - chemistry</subject><subject>Epitopes - immunology</subject><subject>Fibrin</subject><subject>Fibrin - chemistry</subject><subject>Fibrin - immunology</subject><subject>Fibrin - metabolism</subject><subject>Fibrinogen - chemistry</subject><subject>Fibrinogen - immunology</subject><subject>Fibrinogen - metabolism</subject><subject>Humans</subject><subject>Intermediate Filament Proteins - immunology</subject><subject>Intermediate Filament Proteins - metabolism</subject><subject>Life Sciences</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Protein Structure, Quaternary</subject><subject>Rheumatoid arthritis</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNp9kMFO3DAQQK2Kqiy0R67IH0Cox3ES-4jQtlCt1Et7tpxk0gzKxpHtBS0nPqHf2C_BaBHcerJGfvM0eoydgbgEIeRXvKNLKURVVo0RH9gKKgmFAgVHbCUEqEIaLY7ZSYx3QghTV-YTO4Zal1o2esXieqHkF4zcD3zcbd3MB2oDzTxg5__M9Ig9b_c8jcjDiBlInnruQhoDJYr_nv7GBTsaqONul7ybE7W-pyxMnneUwm6aaHYpa5bgE9IcP7OPg5sifnl9T9nvb-tf1zfF5uf32-urTdGpSohCdcZpKesaWqjBYK8Ho4b807xMDWhUZdVX2oDupTQNlmXX1n2DSlVlrVR5yi4O3tFNdgm0dWFvvSN7c7Wx-Q4MWysUNGA03EPGiwPeBR9jwOFtB4R9aW1za_vWOvPnB37ZtVvs3-nXuBloDsADTbj_v82uf9y-q58B_kWMaA</recordid><startdate>200608</startdate><enddate>200608</enddate><creator>Sebbag, Mireille</creator><creator>Moinard, Nathalie</creator><creator>Auger, Isabelle</creator><creator>Clavel, Cyril</creator><creator>Arnaud, Jacques</creator><creator>Nogueira, Leonor</creator><creator>Roudier, Jean</creator><creator>Serre, Guy</creator><general>WILEY‐VCH Verlag</general><general>Wiley-VCH Verlag</general><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>1XC</scope></search><sort><creationdate>200608</creationdate><title>Epitopes of human fibrin recognized by the rheumatoid arthritis‐specific autoantibodies to citrullinated proteins</title><author>Sebbag, Mireille ; Moinard, Nathalie ; Auger, Isabelle ; Clavel, Cyril ; Arnaud, Jacques ; Nogueira, Leonor ; Roudier, Jean ; Serre, Guy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4500-4c9a822661b1619ed8f94f5007619e718e435d58918d2297e33cb6d7e44536443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Amino Acid Sequence</topic><topic>Antibody Specificity</topic><topic>Anti‐citrullinated protein autoantibodies</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Arthritis, Rheumatoid - metabolism</topic><topic>Autoantibodies - immunology</topic><topic>Citrulline</topic><topic>Citrulline - immunology</topic><topic>Citrulline - metabolism</topic><topic>Deimination</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epitopes - chemistry</topic><topic>Epitopes - immunology</topic><topic>Fibrin</topic><topic>Fibrin - chemistry</topic><topic>Fibrin - immunology</topic><topic>Fibrin - metabolism</topic><topic>Fibrinogen - chemistry</topic><topic>Fibrinogen - immunology</topic><topic>Fibrinogen - metabolism</topic><topic>Humans</topic><topic>Intermediate Filament Proteins - immunology</topic><topic>Intermediate Filament Proteins - metabolism</topic><topic>Life Sciences</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Protein Structure, Quaternary</topic><topic>Rheumatoid arthritis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sebbag, Mireille</creatorcontrib><creatorcontrib>Moinard, Nathalie</creatorcontrib><creatorcontrib>Auger, Isabelle</creatorcontrib><creatorcontrib>Clavel, Cyril</creatorcontrib><creatorcontrib>Arnaud, Jacques</creatorcontrib><creatorcontrib>Nogueira, Leonor</creatorcontrib><creatorcontrib>Roudier, Jean</creatorcontrib><creatorcontrib>Serre, Guy</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>European journal of immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sebbag, Mireille</au><au>Moinard, Nathalie</au><au>Auger, Isabelle</au><au>Clavel, Cyril</au><au>Arnaud, Jacques</au><au>Nogueira, Leonor</au><au>Roudier, Jean</au><au>Serre, Guy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epitopes of human fibrin recognized by the rheumatoid arthritis‐specific autoantibodies to citrullinated proteins</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>2006-08</date><risdate>2006</risdate><volume>36</volume><issue>8</issue><spage>2250</spage><epage>2263</epage><pages>2250-2263</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><notes>These two authors contributed equally to this paper.</notes><abstract>Formation of the epitopes recognized by the rheumatoid arthritis (RA)‐specific autoantibodies to citrullinated proteins (ACPA) on filaggrin and on the α‐ and β‐chains of fibrin, their synovial target, requires conversion of their arginyl residues into citrullyl residues, but is also affected by their amino‐acyl environment. Using competition with five citrullinated filaggrin‐derived peptides bearing major ACPA epitopes, we confirmed the close cross‐reactivity between filaggrin and citrullinated fibrin. To identify the sequential epitopes recognized on fibrin by ACPA, 71 citrullinated 15‐mer peptides derived from all the sites of the α‐ and β‐chains of fibrin harboring arginyl residues were tested by ELISA using ACPA‐positive RA sera exhibiting different reactivity profiles to the five filaggrin peptides. We identified 18 fibrin‐derived peptides bearing ACPA epitopes. Regarding the ability of fibrinogen arginyl residues to be citrullinated in vitro, 11 of the peptides likely correspond to in vivo targeted epitopes. Two out of them bear major epitopes and are located in the central globular domain of the protein. In the synovial tissue, fibrin citrullination and ACPA binding could impair fibrin degradation by plasmin. The immunological conflict between ACPA and fibrin could therefore sustain synovial inflammation not only via pro‐inflammatory effector mechanisms but also via impairment of fibrinolysis.</abstract><cop>Weinheim</cop><pub>WILEY‐VCH Verlag</pub><pmid>16838278</pmid><doi>10.1002/eji.200535790</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | European journal of immunology, 2006-08, Vol.36 (8), p.2250-2263 |
| issn | 0014-2980 1521-4141 |
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| source | Wiley |
| subjects | Amino Acid Sequence Antibody Specificity Anti‐citrullinated protein autoantibodies Arthritis, Rheumatoid - immunology Arthritis, Rheumatoid - metabolism Autoantibodies - immunology Citrulline Citrulline - immunology Citrulline - metabolism Deimination Enzyme-Linked Immunosorbent Assay Epitopes - chemistry Epitopes - immunology Fibrin Fibrin - chemistry Fibrin - immunology Fibrin - metabolism Fibrinogen - chemistry Fibrinogen - immunology Fibrinogen - metabolism Humans Intermediate Filament Proteins - immunology Intermediate Filament Proteins - metabolism Life Sciences Models, Molecular Molecular Sequence Data Protein Structure, Quaternary Rheumatoid arthritis |
| title | Epitopes of human fibrin recognized by the rheumatoid arthritis‐specific autoantibodies to citrullinated proteins |
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