Mapping of topoisomerase II α epitopes recognized by autoantibodies in idiopathic pulmonary fibrosis
Autoantibodies against DNA topoisomerase II α have been identified in the sera of patients with idiopathic pulmonary fibrosis (IPF). To map topoisomerase II autoepitopes, we tested by ELISA and immunoblotting the IPF anti‐topoisomerase II‐positive sera against a series of recombinant proteins which...
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| Veröffentlicht in: | Clinical and experimental immunology 1998-12, Vol.114 (3), p.339-346 |
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| creator | GRIGOLO, B MAZZETTI, I BORZI, R. M HICKSON, I. D FABBRI, M FASANO, L MELICONI, R FACCHINI, A |
| description | Autoantibodies against DNA topoisomerase II α have been identified in the sera of patients with idiopathic pulmonary fibrosis (IPF). To map topoisomerase II autoepitopes, we tested by ELISA and immunoblotting the IPF anti‐topoisomerase II‐positive sera against a series of recombinant proteins which covered the full length of topoisomerase II α. Specific patterns of reactivity were observed, indicating the existence of multiple epitopes on topoisomerase II, either highly complex or conformational/discontiguous or conformational/contiguous ones. The latter resided in amino acid residues 854–1147 and 1370–1447. A detailed analysis of these regions was undertaken, but we were not able to pinpoint a sequential peptide‐sized epitope, or any significant homology with foreign pathogens. Further, we observed a significant correlation between the progression from a contiguous to a quaternary/tertiary structure‐dependent autoepitope and the disease duration but not with the disease severity. Therefore, this result supports the hypothesis that anti‐topoisomerase II autoreactivity evolves following an antigen‐driven process. |
| doi_str_mv | 10.1046/j.1365-2249.1998.00747.x |
| format | Article |
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M ; HICKSON, I. D ; FABBRI, M ; FASANO, L ; MELICONI, R ; FACCHINI, A</creator><creatorcontrib>GRIGOLO, B ; MAZZETTI, I ; BORZI, R. M ; HICKSON, I. D ; FABBRI, M ; FASANO, L ; MELICONI, R ; FACCHINI, A</creatorcontrib><description>Autoantibodies against DNA topoisomerase II α have been identified in the sera of patients with idiopathic pulmonary fibrosis (IPF). To map topoisomerase II autoepitopes, we tested by ELISA and immunoblotting the IPF anti‐topoisomerase II‐positive sera against a series of recombinant proteins which covered the full length of topoisomerase II α. Specific patterns of reactivity were observed, indicating the existence of multiple epitopes on topoisomerase II, either highly complex or conformational/discontiguous or conformational/contiguous ones. The latter resided in amino acid residues 854–1147 and 1370–1447. A detailed analysis of these regions was undertaken, but we were not able to pinpoint a sequential peptide‐sized epitope, or any significant homology with foreign pathogens. Further, we observed a significant correlation between the progression from a contiguous to a quaternary/tertiary structure‐dependent autoepitope and the disease duration but not with the disease severity. Therefore, this result supports the hypothesis that anti‐topoisomerase II autoreactivity evolves following an antigen‐driven process.</description><identifier>ISSN: 0009-9104</identifier><identifier>EISSN: 1365-2249</identifier><identifier>DOI: 10.1046/j.1365-2249.1998.00747.x</identifier><identifier>PMID: 9844041</identifier><identifier>CODEN: CEXIAL</identifier><language>eng</language><publisher>Oxford BSL: Blackwell Science Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; autoantibodies ; Autoantibodies - blood ; Autoantibodies - immunology ; Biological and medical sciences ; DNA Topoisomerases, Type II - immunology ; DNA-Binding Proteins ; Epitope Mapping ; Epitopes, B-Lymphocyte - immunology ; Female ; Humans ; idiopathic pulmonary fibrosis ; Isoenzymes - immunology ; Male ; Medical sciences ; Middle Aged ; Original ; Pneumology ; Pulmonary Fibrosis - blood ; Pulmonary Fibrosis - immunology ; Respiratory system : syndromes and miscellaneous diseases ; topoisomerase II</subject><ispartof>Clinical and experimental immunology, 1998-12, Vol.114 (3), p.339-346</ispartof><rights>Blackwell Science Ltd, Oxford</rights><rights>1999 INIST-CNRS</rights><rights>1998 Blackwell Science Ltd 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4977-a219c78092b219665a85a50255f1d4d02a08f0f97327671ed052d76be8d8164e3</citedby><cites>FETCH-LOGICAL-c4977-a219c78092b219665a85a50255f1d4d02a08f0f97327671ed052d76be8d8164e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905127/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905127/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1589732$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9844041$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GRIGOLO, B</creatorcontrib><creatorcontrib>MAZZETTI, I</creatorcontrib><creatorcontrib>BORZI, R. M</creatorcontrib><creatorcontrib>HICKSON, I. D</creatorcontrib><creatorcontrib>FABBRI, M</creatorcontrib><creatorcontrib>FASANO, L</creatorcontrib><creatorcontrib>MELICONI, R</creatorcontrib><creatorcontrib>FACCHINI, A</creatorcontrib><title>Mapping of topoisomerase II α epitopes recognized by autoantibodies in idiopathic pulmonary fibrosis</title><title>Clinical and experimental immunology</title><addtitle>Clin Exp Immunol</addtitle><description>Autoantibodies against DNA topoisomerase II α have been identified in the sera of patients with idiopathic pulmonary fibrosis (IPF). To map topoisomerase II autoepitopes, we tested by ELISA and immunoblotting the IPF anti‐topoisomerase II‐positive sera against a series of recombinant proteins which covered the full length of topoisomerase II α. Specific patterns of reactivity were observed, indicating the existence of multiple epitopes on topoisomerase II, either highly complex or conformational/discontiguous or conformational/contiguous ones. The latter resided in amino acid residues 854–1147 and 1370–1447. A detailed analysis of these regions was undertaken, but we were not able to pinpoint a sequential peptide‐sized epitope, or any significant homology with foreign pathogens. Further, we observed a significant correlation between the progression from a contiguous to a quaternary/tertiary structure‐dependent autoepitope and the disease duration but not with the disease severity. Therefore, this result supports the hypothesis that anti‐topoisomerase II autoreactivity evolves following an antigen‐driven process.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens, Neoplasm</subject><subject>autoantibodies</subject><subject>Autoantibodies - blood</subject><subject>Autoantibodies - immunology</subject><subject>Biological and medical sciences</subject><subject>DNA Topoisomerases, Type II - immunology</subject><subject>DNA-Binding Proteins</subject><subject>Epitope Mapping</subject><subject>Epitopes, B-Lymphocyte - immunology</subject><subject>Female</subject><subject>Humans</subject><subject>idiopathic pulmonary fibrosis</subject><subject>Isoenzymes - immunology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Original</subject><subject>Pneumology</subject><subject>Pulmonary Fibrosis - blood</subject><subject>Pulmonary Fibrosis - immunology</subject><subject>Respiratory system : syndromes and miscellaneous diseases</subject><subject>topoisomerase II</subject><issn>0009-9104</issn><issn>1365-2249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUcuO0zAUtRBoKAOfgOQFYpdgu35KCAlVA1QaxAbWlmM7HVeJHeJkmPJX_Mh80zi0KrBj5et7HvfaBwCIUY0R5W_2NV5zVhFCVY2VkjVCgor67hFYnYHHYIUQUpUqiqfgWc77cuWckwtwoSSliOIV8J_NMIS4g6mFUxpSyKn3o8kebrfw_hf0Qyhtn-HobdrF8NM72Bygmadk4hSa5EIBQ4TBhTSY6SZYOMxdn6IZD7ANzZhyyM_Bk9Z02b84nZfg24err5tP1fWXj9vN--vKUiVEZQhWVkikSFMqzpmRzDBEGGuxow4Rg2SLWiXWRHCBvUOMOMEbL53EnPr1JXh39B3mpvfO-jiNptPDGPqyjk4m6H-RGG70Lt1qrBDDRBSD1yeDMX2ffZ50H7L1XWeiT3PWAmHMqMSFKI9EWx6YR9-eh2Ckl4j0Xi9J6CUJvUSkf0ek74r05d9LnoWnTAr-6oSbbE3XjibakP_4M7l8QKG9PdJ-hM4f_nu83lxtS7F-AMvprvE</recordid><startdate>199812</startdate><enddate>199812</enddate><creator>GRIGOLO, B</creator><creator>MAZZETTI, I</creator><creator>BORZI, R. M</creator><creator>HICKSON, I. D</creator><creator>FABBRI, M</creator><creator>FASANO, L</creator><creator>MELICONI, R</creator><creator>FACCHINI, A</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><general>Blackwell Publishing Ltd</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><scope>5PM</scope></search><sort><creationdate>199812</creationdate><title>Mapping of topoisomerase II α epitopes recognized by autoantibodies in idiopathic pulmonary fibrosis</title><author>GRIGOLO, B ; MAZZETTI, I ; BORZI, R. M ; HICKSON, I. D ; FABBRI, M ; FASANO, L ; MELICONI, R ; FACCHINI, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4977-a219c78092b219665a85a50255f1d4d02a08f0f97327671ed052d76be8d8164e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antigens, Neoplasm</topic><topic>autoantibodies</topic><topic>Autoantibodies - blood</topic><topic>Autoantibodies - immunology</topic><topic>Biological and medical sciences</topic><topic>DNA Topoisomerases, Type II - immunology</topic><topic>DNA-Binding Proteins</topic><topic>Epitope Mapping</topic><topic>Epitopes, B-Lymphocyte - immunology</topic><topic>Female</topic><topic>Humans</topic><topic>idiopathic pulmonary fibrosis</topic><topic>Isoenzymes - immunology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Original</topic><topic>Pneumology</topic><topic>Pulmonary Fibrosis - blood</topic><topic>Pulmonary Fibrosis - immunology</topic><topic>Respiratory system : syndromes and miscellaneous diseases</topic><topic>topoisomerase II</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GRIGOLO, B</creatorcontrib><creatorcontrib>MAZZETTI, I</creatorcontrib><creatorcontrib>BORZI, R. M</creatorcontrib><creatorcontrib>HICKSON, I. D</creatorcontrib><creatorcontrib>FABBRI, M</creatorcontrib><creatorcontrib>FASANO, L</creatorcontrib><creatorcontrib>MELICONI, R</creatorcontrib><creatorcontrib>FACCHINI, A</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical and experimental immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GRIGOLO, B</au><au>MAZZETTI, I</au><au>BORZI, R. M</au><au>HICKSON, I. D</au><au>FABBRI, M</au><au>FASANO, L</au><au>MELICONI, R</au><au>FACCHINI, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mapping of topoisomerase II α epitopes recognized by autoantibodies in idiopathic pulmonary fibrosis</atitle><jtitle>Clinical and experimental immunology</jtitle><addtitle>Clin Exp Immunol</addtitle><date>1998-12</date><risdate>1998</risdate><volume>114</volume><issue>3</issue><spage>339</spage><epage>346</epage><pages>339-346</pages><issn>0009-9104</issn><eissn>1365-2249</eissn><coden>CEXIAL</coden><abstract>Autoantibodies against DNA topoisomerase II α have been identified in the sera of patients with idiopathic pulmonary fibrosis (IPF). To map topoisomerase II autoepitopes, we tested by ELISA and immunoblotting the IPF anti‐topoisomerase II‐positive sera against a series of recombinant proteins which covered the full length of topoisomerase II α. Specific patterns of reactivity were observed, indicating the existence of multiple epitopes on topoisomerase II, either highly complex or conformational/discontiguous or conformational/contiguous ones. The latter resided in amino acid residues 854–1147 and 1370–1447. A detailed analysis of these regions was undertaken, but we were not able to pinpoint a sequential peptide‐sized epitope, or any significant homology with foreign pathogens. Further, we observed a significant correlation between the progression from a contiguous to a quaternary/tertiary structure‐dependent autoepitope and the disease duration but not with the disease severity. Therefore, this result supports the hypothesis that anti‐topoisomerase II autoreactivity evolves following an antigen‐driven process.</abstract><cop>Oxford BSL</cop><pub>Blackwell Science Ltd</pub><pmid>9844041</pmid><doi>10.1046/j.1365-2249.1998.00747.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical and experimental immunology, 1998-12, Vol.114 (3), p.339-346 |
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| language | eng |
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| subjects | Adult Aged Aged, 80 and over Antigens, Neoplasm autoantibodies Autoantibodies - blood Autoantibodies - immunology Biological and medical sciences DNA Topoisomerases, Type II - immunology DNA-Binding Proteins Epitope Mapping Epitopes, B-Lymphocyte - immunology Female Humans idiopathic pulmonary fibrosis Isoenzymes - immunology Male Medical sciences Middle Aged Original Pneumology Pulmonary Fibrosis - blood Pulmonary Fibrosis - immunology Respiratory system : syndromes and miscellaneous diseases topoisomerase II |
| title | Mapping of topoisomerase II α epitopes recognized by autoantibodies in idiopathic pulmonary fibrosis |
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