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Spreading of antibody reactivity to non‐thyroid antigens during experimental immunization with human thyroglobulin
Summary Intermolecular spreading of antibody reactivity has been implicated in the evolution of autoimmune disease. In this study, spreading of antibody reactivity to non‐thyroid autoantigens after experimental immunization with thyroglobulin (Tg) was investigated. For this purpose, two rabbits were...
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| Published in: | Clinical and experimental immunology 2007-01, Vol.147 (1), p.120-127 |
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| container_end_page | 127 |
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| container_title | Clinical and experimental immunology |
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| creator | Thrasyvoulides, A. Liakata, E. Lymberi, P. |
| description | Summary
Intermolecular spreading of antibody reactivity has been implicated in the evolution of autoimmune disease. In this study, spreading of antibody reactivity to non‐thyroid autoantigens after experimental immunization with thyroglobulin (Tg) was investigated. For this purpose, two rabbits were injected with human Tg six times (stages 1–6) every 3 weeks. Animals were also bled before priming. Antisera were tested by enzyme‐linked immunosorbent assay (ELISA) for reactivity to several non‐thyroid antigens: bovine serum albumin (BSA), native DNA (nDNA), human myosin, human globular (G) and filamentous (F) actin and porcine tubulin. Tg‐immunized animals developed the following serological reactivity pattern: (a) high reactivity to myosin from stage 2 onward, (b) significant reactivity to F‐actin, remaining high up to stage 6, (c) reactivity to BSA with a peak at stage 3, (d) a small increase of reactivity to G‐actin at stage 3 and (e) no increase of reactivity to nDNA and tubulin. The study of affinity‐purified anti‐Tg antibodies and the use of competitive assays revealed that reactivity to F‐actin was not due to cross‐reaction with Tg. On the contrary, reactivity to myosin during the first stages of immunization was due to cross‐reaction with Tg, while at stage 6 it became myosin‐specific. Reactivity to BSA at stage 3 was also due to cross‐reaction with Tg. We conclude that at least part of the induced anti‐Tg antibodies may result from the expansion of B cell clones producing polyreactive natural autoantibodies, and polyreactivity of anti‐Tg antibodies during the first stages of Tg‐immunization may be responsible for the intermolecular spreading of antibody response. |
| doi_str_mv | 10.1111/j.1365-2249.2006.03246.x |
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Intermolecular spreading of antibody reactivity has been implicated in the evolution of autoimmune disease. In this study, spreading of antibody reactivity to non‐thyroid autoantigens after experimental immunization with thyroglobulin (Tg) was investigated. For this purpose, two rabbits were injected with human Tg six times (stages 1–6) every 3 weeks. Animals were also bled before priming. Antisera were tested by enzyme‐linked immunosorbent assay (ELISA) for reactivity to several non‐thyroid antigens: bovine serum albumin (BSA), native DNA (nDNA), human myosin, human globular (G) and filamentous (F) actin and porcine tubulin. Tg‐immunized animals developed the following serological reactivity pattern: (a) high reactivity to myosin from stage 2 onward, (b) significant reactivity to F‐actin, remaining high up to stage 6, (c) reactivity to BSA with a peak at stage 3, (d) a small increase of reactivity to G‐actin at stage 3 and (e) no increase of reactivity to nDNA and tubulin. The study of affinity‐purified anti‐Tg antibodies and the use of competitive assays revealed that reactivity to F‐actin was not due to cross‐reaction with Tg. On the contrary, reactivity to myosin during the first stages of immunization was due to cross‐reaction with Tg, while at stage 6 it became myosin‐specific. Reactivity to BSA at stage 3 was also due to cross‐reaction with Tg. We conclude that at least part of the induced anti‐Tg antibodies may result from the expansion of B cell clones producing polyreactive natural autoantibodies, and polyreactivity of anti‐Tg antibodies during the first stages of Tg‐immunization may be responsible for the intermolecular spreading of antibody response.</description><identifier>ISSN: 0009-9104</identifier><identifier>EISSN: 1365-2249</identifier><identifier>DOI: 10.1111/j.1365-2249.2006.03246.x</identifier><identifier>PMID: 17177971</identifier><identifier>CODEN: CEXIAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Actins - immunology ; Animal Studies ; Animals ; Antibodies - blood ; Antibody Formation ; Antibody Specificity ; Antigens - immunology ; Autoantibodies - blood ; Biological and medical sciences ; Cross Reactions ; Enzyme-Linked Immunosorbent Assay - methods ; Epitopes ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Humans ; Immunization - methods ; Immunopathology ; Immunosorbent Techniques ; intermolecular epitope spreading ; Medical sciences ; Myosins - immunology ; polyreactive antibodies ; Protein Conformation ; Rabbits ; Serum Albumin, Bovine - immunology ; thyroglobulin ; Thyroglobulin - pharmacology</subject><ispartof>Clinical and experimental immunology, 2007-01, Vol.147 (1), p.120-127</ispartof><rights>2007 INIST-CNRS</rights><rights>Copyright Blackwell Publishing Jan 2007</rights><rights>2006 British Society for Immunology 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5606-918ebac47be993e966d53a824285b140585e719990da77665a37d9701448252c3</citedby><cites>FETCH-LOGICAL-c5606-918ebac47be993e966d53a824285b140585e719990da77665a37d9701448252c3</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/PMC1810443/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810443/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18488180$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17177971$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thrasyvoulides, A.</creatorcontrib><creatorcontrib>Liakata, E.</creatorcontrib><creatorcontrib>Lymberi, P.</creatorcontrib><title>Spreading of antibody reactivity to non‐thyroid antigens during experimental immunization with human thyroglobulin</title><title>Clinical and experimental immunology</title><addtitle>Clin Exp Immunol</addtitle><description>Summary
Intermolecular spreading of antibody reactivity has been implicated in the evolution of autoimmune disease. In this study, spreading of antibody reactivity to non‐thyroid autoantigens after experimental immunization with thyroglobulin (Tg) was investigated. For this purpose, two rabbits were injected with human Tg six times (stages 1–6) every 3 weeks. Animals were also bled before priming. Antisera were tested by enzyme‐linked immunosorbent assay (ELISA) for reactivity to several non‐thyroid antigens: bovine serum albumin (BSA), native DNA (nDNA), human myosin, human globular (G) and filamentous (F) actin and porcine tubulin. Tg‐immunized animals developed the following serological reactivity pattern: (a) high reactivity to myosin from stage 2 onward, (b) significant reactivity to F‐actin, remaining high up to stage 6, (c) reactivity to BSA with a peak at stage 3, (d) a small increase of reactivity to G‐actin at stage 3 and (e) no increase of reactivity to nDNA and tubulin. The study of affinity‐purified anti‐Tg antibodies and the use of competitive assays revealed that reactivity to F‐actin was not due to cross‐reaction with Tg. On the contrary, reactivity to myosin during the first stages of immunization was due to cross‐reaction with Tg, while at stage 6 it became myosin‐specific. Reactivity to BSA at stage 3 was also due to cross‐reaction with Tg. We conclude that at least part of the induced anti‐Tg antibodies may result from the expansion of B cell clones producing polyreactive natural autoantibodies, and polyreactivity of anti‐Tg antibodies during the first stages of Tg‐immunization may be responsible for the intermolecular spreading of antibody response.</description><subject>Actins - immunology</subject><subject>Animal Studies</subject><subject>Animals</subject><subject>Antibodies - blood</subject><subject>Antibody Formation</subject><subject>Antibody Specificity</subject><subject>Antigens - immunology</subject><subject>Autoantibodies - blood</subject><subject>Biological and medical sciences</subject><subject>Cross Reactions</subject><subject>Enzyme-Linked Immunosorbent Assay - methods</subject><subject>Epitopes</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Humans</subject><subject>Immunization - methods</subject><subject>Immunopathology</subject><subject>Immunosorbent Techniques</subject><subject>intermolecular epitope spreading</subject><subject>Medical sciences</subject><subject>Myosins - immunology</subject><subject>polyreactive antibodies</subject><subject>Protein Conformation</subject><subject>Rabbits</subject><subject>Serum Albumin, Bovine - immunology</subject><subject>thyroglobulin</subject><subject>Thyroglobulin - pharmacology</subject><issn>0009-9104</issn><issn>1365-2249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNqNkstuEzEUhi0EoqHwCshCgl0Ge3xfgFRFBSpVYgGsLc-MkziasYPtaRNWPALPyJPgSaIW2IA3vpzvP_p9zgEAYlThsl5vKkw4m9c1VVWNEK8QqSmvdg_A7C7wEMwQQmquMKJn4ElKm3LlnNePwRkWWAgl8AzkT9toTef8CoYlND67JnR7WN7a7G5c3sMcoA_-5_cfeb2PwXUHaGV9gt0YJ53dbW10g_XZ9NANw-jdN5Nd8PDW5TVcj4Px8CBe9aEZe-efgkdL0yf77LSfgy_vLj8vPsyvP76_Wlxcz1vGES_OpW1MS0VjlSJWcd4xYmRNa8kaTBGTzAqslEKdEYJzZojolECYUlmzuiXn4O0x73ZsBtu1xWI0vd4WtybudTBO_xnxbq1X4UZjWYpGSUnw6pQghq-jTVkPLrW27423YUyaSyKJYv8GsWKcIMkK-OIvcBPG6EsVCsOlRIKoAskj1MaQUrTLO8sY6WkA9EZPfdZTn_U0APowAHpXpM9___K98NTxArw8ASa1pl9G41uX7jlJpcQSFe7Nkbt1vd3_twG9uLyaTuQXTwfPDw</recordid><startdate>200701</startdate><enddate>200701</enddate><creator>Thrasyvoulides, A.</creator><creator>Liakata, E.</creator><creator>Lymberi, P.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><general>Oxford University Press</general><general>Blackwell Science Inc</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>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>M7N</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200701</creationdate><title>Spreading of antibody reactivity to non‐thyroid antigens during experimental immunization with human thyroglobulin</title><author>Thrasyvoulides, A. ; Liakata, E. ; Lymberi, P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5606-918ebac47be993e966d53a824285b140585e719990da77665a37d9701448252c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Actins - immunology</topic><topic>Animal Studies</topic><topic>Animals</topic><topic>Antibodies - blood</topic><topic>Antibody Formation</topic><topic>Antibody Specificity</topic><topic>Antigens - immunology</topic><topic>Autoantibodies - blood</topic><topic>Biological and medical sciences</topic><topic>Cross Reactions</topic><topic>Enzyme-Linked Immunosorbent Assay - methods</topic><topic>Epitopes</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Humans</topic><topic>Immunization - methods</topic><topic>Immunopathology</topic><topic>Immunosorbent Techniques</topic><topic>intermolecular epitope spreading</topic><topic>Medical sciences</topic><topic>Myosins - immunology</topic><topic>polyreactive antibodies</topic><topic>Protein Conformation</topic><topic>Rabbits</topic><topic>Serum Albumin, Bovine - immunology</topic><topic>thyroglobulin</topic><topic>Thyroglobulin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thrasyvoulides, A.</creatorcontrib><creatorcontrib>Liakata, E.</creatorcontrib><creatorcontrib>Lymberi, P.</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>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</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>Thrasyvoulides, A.</au><au>Liakata, E.</au><au>Lymberi, P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spreading of antibody reactivity to non‐thyroid antigens during experimental immunization with human thyroglobulin</atitle><jtitle>Clinical and experimental immunology</jtitle><addtitle>Clin Exp Immunol</addtitle><date>2007-01</date><risdate>2007</risdate><volume>147</volume><issue>1</issue><spage>120</spage><epage>127</epage><pages>120-127</pages><issn>0009-9104</issn><eissn>1365-2249</eissn><coden>CEXIAL</coden><abstract>Summary
Intermolecular spreading of antibody reactivity has been implicated in the evolution of autoimmune disease. In this study, spreading of antibody reactivity to non‐thyroid autoantigens after experimental immunization with thyroglobulin (Tg) was investigated. For this purpose, two rabbits were injected with human Tg six times (stages 1–6) every 3 weeks. Animals were also bled before priming. Antisera were tested by enzyme‐linked immunosorbent assay (ELISA) for reactivity to several non‐thyroid antigens: bovine serum albumin (BSA), native DNA (nDNA), human myosin, human globular (G) and filamentous (F) actin and porcine tubulin. Tg‐immunized animals developed the following serological reactivity pattern: (a) high reactivity to myosin from stage 2 onward, (b) significant reactivity to F‐actin, remaining high up to stage 6, (c) reactivity to BSA with a peak at stage 3, (d) a small increase of reactivity to G‐actin at stage 3 and (e) no increase of reactivity to nDNA and tubulin. The study of affinity‐purified anti‐Tg antibodies and the use of competitive assays revealed that reactivity to F‐actin was not due to cross‐reaction with Tg. On the contrary, reactivity to myosin during the first stages of immunization was due to cross‐reaction with Tg, while at stage 6 it became myosin‐specific. Reactivity to BSA at stage 3 was also due to cross‐reaction with Tg. We conclude that at least part of the induced anti‐Tg antibodies may result from the expansion of B cell clones producing polyreactive natural autoantibodies, and polyreactivity of anti‐Tg antibodies during the first stages of Tg‐immunization may be responsible for the intermolecular spreading of antibody response.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>17177971</pmid><doi>10.1111/j.1365-2249.2006.03246.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical and experimental immunology, 2007-01, Vol.147 (1), p.120-127 |
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| subjects | Actins - immunology Animal Studies Animals Antibodies - blood Antibody Formation Antibody Specificity Antigens - immunology Autoantibodies - blood Biological and medical sciences Cross Reactions Enzyme-Linked Immunosorbent Assay - methods Epitopes Fundamental and applied biological sciences. Psychology Fundamental immunology Humans Immunization - methods Immunopathology Immunosorbent Techniques intermolecular epitope spreading Medical sciences Myosins - immunology polyreactive antibodies Protein Conformation Rabbits Serum Albumin, Bovine - immunology thyroglobulin Thyroglobulin - pharmacology |
| title | Spreading of antibody reactivity to non‐thyroid antigens during experimental immunization with human thyroglobulin |
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