Anti-SLA/LP alone or in combination with anti-Ro52 and fine specificity of anti-Ro52 antibodies in patients with autoimmune hepatitis

Background & Aims Antibodies (Abs) to soluble liver antigen/liver pancreas (anti‐SLA/LP) are considered markers of worse prognosis and outcome in patients with autoimmune hepatitis (AIH) although this assumption has recently been attributed to their frequent co‐expression with Abs against Ro52 (...

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Veröffentlicht in:Liver international 2015-02, Vol.35 (2), p.660-672
Hauptverfasser: Zachou, Kalliopi, Gampeta, Stella, Gatselis, Nikolaos K., Oikonomou, Katerina, Goulis, John, Manoussakis, Menelaos N., Renaudineau, Yves, Bogdanos, Dimitrios P., Dalekos, George N.
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container_end_page 672
container_issue 2
container_start_page 660
container_title Liver international
container_volume 35
creator Zachou, Kalliopi
Gampeta, Stella
Gatselis, Nikolaos K.
Oikonomou, Katerina
Goulis, John
Manoussakis, Menelaos N.
Renaudineau, Yves
Bogdanos, Dimitrios P.
Dalekos, George N.
description Background & Aims Antibodies (Abs) to soluble liver antigen/liver pancreas (anti‐SLA/LP) are considered markers of worse prognosis and outcome in patients with autoimmune hepatitis (AIH) although this assumption has recently been attributed to their frequent co‐expression with Abs against Ro52 (anti‐Ro52). To assess the clinical significance of anti‐SLA/LP Abs alone or in combination with anti‐Ro52 in AIH patients and determine the immunodominant Ro52 epitopes according to the anti‐SLA/LP status. Methods Twenty‐three anti‐SLA/LP‐positive and 106 anti‐SLA/LP‐negative AIH patients were included. Anti‐SLA/LP were determined by ELISA using recombinant antigen, and confirmed by immunoblot using cytosolic rat liver fraction or HuH‐7 extract. Anti‐Ro52 Abs were determined by ELISA using recombinant antigen. Epitope mapping was assessed by ELISA using overlapping peptides covering the whole Ro52 protein in 26 AIH patients and 12 patients with Sjögren's syndrome. Results Anti‐SLA/LP positivity was not associated with the clinical, laboratory or histological characteristics of AIH patients. Treatment response, corticosteroid withdrawal, relapse after stopping treatment and outcome, were not associated with the presence of anti‐SLA/LP, anti‐Ro52 or double reactivity. Moreover, Ro52 epitope mapping revealed new epitopes unique for AIH and independent from anti‐SLA/LP positivity. Conclusions Neither anti‐SLA/LP nor anti‐Ro52 Abs or their combination could specify a distinct group of AIH patients in terms of clinical characteristics, treatment response and outcome. Further studies are needed to clarify whether the newly discovered immunodominant epitopes of Ro52 antigen which were associated specifically with AIH have any clinical or pathogenetic significance in AIH.
doi_str_mv 10.1111/liv.12658
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To assess the clinical significance of anti‐SLA/LP Abs alone or in combination with anti‐Ro52 in AIH patients and determine the immunodominant Ro52 epitopes according to the anti‐SLA/LP status. Methods Twenty‐three anti‐SLA/LP‐positive and 106 anti‐SLA/LP‐negative AIH patients were included. Anti‐SLA/LP were determined by ELISA using recombinant antigen, and confirmed by immunoblot using cytosolic rat liver fraction or HuH‐7 extract. Anti‐Ro52 Abs were determined by ELISA using recombinant antigen. Epitope mapping was assessed by ELISA using overlapping peptides covering the whole Ro52 protein in 26 AIH patients and 12 patients with Sjögren's syndrome. Results Anti‐SLA/LP positivity was not associated with the clinical, laboratory or histological characteristics of AIH patients. Treatment response, corticosteroid withdrawal, relapse after stopping treatment and outcome, were not associated with the presence of anti‐SLA/LP, anti‐Ro52 or double reactivity. Moreover, Ro52 epitope mapping revealed new epitopes unique for AIH and independent from anti‐SLA/LP positivity. Conclusions Neither anti‐SLA/LP nor anti‐Ro52 Abs or their combination could specify a distinct group of AIH patients in terms of clinical characteristics, treatment response and outcome. Further studies are needed to clarify whether the newly discovered immunodominant epitopes of Ro52 antigen which were associated specifically with AIH have any clinical or pathogenetic significance in AIH.</description><identifier>ISSN: 1478-3223</identifier><identifier>EISSN: 1478-3231</identifier><identifier>DOI: 10.1111/liv.12658</identifier><identifier>PMID: 25113420</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>anti-Ro52 antibodies ; anti-SLA/LP antibodies ; Autoantibodies - blood ; Autoantigens - blood ; Autoantigens - immunology ; autoimmune hepatitis ; Biomarkers - blood ; Enzyme-Linked Immunosorbent Assay ; Epitope Mapping ; Greece ; Hepatitis, Autoimmune - blood ; Hepatitis, Autoimmune - classification ; Hepatitis, Autoimmune - immunology ; Humans ; Immunology ; Kaplan-Meier Estimate ; Life Sciences ; Mycophenolic Acid - analogs &amp; derivatives ; Oligonucleotides ; Polymerase Chain Reaction ; Ribonucleoproteins - blood ; Ribonucleoproteins - immunology ; Sjögren's syndrome</subject><ispartof>Liver international, 2015-02, Vol.35 (2), p.660-672</ispartof><rights>2014 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd</rights><rights>2014 John Wiley &amp; Sons A/S. Published by John Wiley &amp; Sons Ltd.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4678-fee353fb98aaa39ffaa2511dd52fb64307c4c31f33d3c25d2e5ddc60d209abf3</citedby><cites>FETCH-LOGICAL-c4678-fee353fb98aaa39ffaa2511dd52fb64307c4c31f33d3c25d2e5ddc60d209abf3</cites><orcidid>0000-0001-5098-5002</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fliv.12658$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fliv.12658$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25113420$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.univ-brest.fr/hal-01068348$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Zachou, Kalliopi</creatorcontrib><creatorcontrib>Gampeta, Stella</creatorcontrib><creatorcontrib>Gatselis, Nikolaos K.</creatorcontrib><creatorcontrib>Oikonomou, Katerina</creatorcontrib><creatorcontrib>Goulis, John</creatorcontrib><creatorcontrib>Manoussakis, Menelaos N.</creatorcontrib><creatorcontrib>Renaudineau, Yves</creatorcontrib><creatorcontrib>Bogdanos, Dimitrios P.</creatorcontrib><creatorcontrib>Dalekos, George N.</creatorcontrib><title>Anti-SLA/LP alone or in combination with anti-Ro52 and fine specificity of anti-Ro52 antibodies in patients with autoimmune hepatitis</title><title>Liver international</title><addtitle>Liver Int</addtitle><description>Background &amp; Aims Antibodies (Abs) to soluble liver antigen/liver pancreas (anti‐SLA/LP) are considered markers of worse prognosis and outcome in patients with autoimmune hepatitis (AIH) although this assumption has recently been attributed to their frequent co‐expression with Abs against Ro52 (anti‐Ro52). To assess the clinical significance of anti‐SLA/LP Abs alone or in combination with anti‐Ro52 in AIH patients and determine the immunodominant Ro52 epitopes according to the anti‐SLA/LP status. Methods Twenty‐three anti‐SLA/LP‐positive and 106 anti‐SLA/LP‐negative AIH patients were included. Anti‐SLA/LP were determined by ELISA using recombinant antigen, and confirmed by immunoblot using cytosolic rat liver fraction or HuH‐7 extract. Anti‐Ro52 Abs were determined by ELISA using recombinant antigen. Epitope mapping was assessed by ELISA using overlapping peptides covering the whole Ro52 protein in 26 AIH patients and 12 patients with Sjögren's syndrome. Results Anti‐SLA/LP positivity was not associated with the clinical, laboratory or histological characteristics of AIH patients. Treatment response, corticosteroid withdrawal, relapse after stopping treatment and outcome, were not associated with the presence of anti‐SLA/LP, anti‐Ro52 or double reactivity. Moreover, Ro52 epitope mapping revealed new epitopes unique for AIH and independent from anti‐SLA/LP positivity. Conclusions Neither anti‐SLA/LP nor anti‐Ro52 Abs or their combination could specify a distinct group of AIH patients in terms of clinical characteristics, treatment response and outcome. Further studies are needed to clarify whether the newly discovered immunodominant epitopes of Ro52 antigen which were associated specifically with AIH have any clinical or pathogenetic significance in AIH.</description><subject>anti-Ro52 antibodies</subject><subject>anti-SLA/LP antibodies</subject><subject>Autoantibodies - blood</subject><subject>Autoantigens - blood</subject><subject>Autoantigens - immunology</subject><subject>autoimmune hepatitis</subject><subject>Biomarkers - blood</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epitope Mapping</subject><subject>Greece</subject><subject>Hepatitis, Autoimmune - blood</subject><subject>Hepatitis, Autoimmune - classification</subject><subject>Hepatitis, Autoimmune - immunology</subject><subject>Humans</subject><subject>Immunology</subject><subject>Kaplan-Meier Estimate</subject><subject>Life Sciences</subject><subject>Mycophenolic Acid - analogs &amp; derivatives</subject><subject>Oligonucleotides</subject><subject>Polymerase Chain Reaction</subject><subject>Ribonucleoproteins - blood</subject><subject>Ribonucleoproteins - immunology</subject><subject>Sjögren's syndrome</subject><issn>1478-3223</issn><issn>1478-3231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctu1DAUhi0EoqXtghdAWcIiHV8zyXKooK2UQkWrlp3l-KI5kMTT2GmZB-C9cZhpJBZ44yP7-z_p6EfoLcGnJJ1FC4-nhBaifIEOCV-WOaOMvJxnyg7QmxB-YEyqSpDX6IAKQhin-BD9XvUR8pt6taivM9X63mZ-yKDPtO8a6FUE32dPENeZmsBvXtA0mcxBIsPGanCgIW4z7_4hIjTegA2TapMsto9h7xmjh64bU35tp68I4Ri9cqoN9mR_H6Hbz59uzy7y-uv55dmqzjUv0irOWiaYa6pSKcUq55SaNjFGUNcUnOGl5poRx5hhmgpDrTBGF9hQXKnGsSP0Yaddq1ZuBujUsJVegbxY1XJ6wwQXJePlI0ns-x27GfzDaEOUHQRt21b11o9BkkJQjjlN_KzVgw9hsG52EyyngmQqSP4tKLHv9tqx6ayZyedGErDYAU_Q2u3_TbK-vHtW5rsEhGh_zQk1_JTFki2FvP9yLit295FfX13J7-wPhByp1A</recordid><startdate>201502</startdate><enddate>201502</enddate><creator>Zachou, Kalliopi</creator><creator>Gampeta, Stella</creator><creator>Gatselis, Nikolaos K.</creator><creator>Oikonomou, Katerina</creator><creator>Goulis, John</creator><creator>Manoussakis, Menelaos N.</creator><creator>Renaudineau, Yves</creator><creator>Bogdanos, Dimitrios P.</creator><creator>Dalekos, George N.</creator><general>Blackwell Publishing Ltd</general><general>Wiley-Blackwell</general><scope>BSCLL</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>1XC</scope><orcidid>https://orcid.org/0000-0001-5098-5002</orcidid></search><sort><creationdate>201502</creationdate><title>Anti-SLA/LP alone or in combination with anti-Ro52 and fine specificity of anti-Ro52 antibodies in patients with autoimmune hepatitis</title><author>Zachou, Kalliopi ; Gampeta, Stella ; Gatselis, Nikolaos K. ; Oikonomou, Katerina ; Goulis, John ; Manoussakis, Menelaos N. ; Renaudineau, Yves ; Bogdanos, Dimitrios P. ; Dalekos, George N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4678-fee353fb98aaa39ffaa2511dd52fb64307c4c31f33d3c25d2e5ddc60d209abf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>anti-Ro52 antibodies</topic><topic>anti-SLA/LP antibodies</topic><topic>Autoantibodies - blood</topic><topic>Autoantigens - blood</topic><topic>Autoantigens - immunology</topic><topic>autoimmune hepatitis</topic><topic>Biomarkers - blood</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epitope Mapping</topic><topic>Greece</topic><topic>Hepatitis, Autoimmune - blood</topic><topic>Hepatitis, Autoimmune - classification</topic><topic>Hepatitis, Autoimmune - immunology</topic><topic>Humans</topic><topic>Immunology</topic><topic>Kaplan-Meier Estimate</topic><topic>Life Sciences</topic><topic>Mycophenolic Acid - analogs &amp; derivatives</topic><topic>Oligonucleotides</topic><topic>Polymerase Chain Reaction</topic><topic>Ribonucleoproteins - blood</topic><topic>Ribonucleoproteins - immunology</topic><topic>Sjögren's syndrome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zachou, Kalliopi</creatorcontrib><creatorcontrib>Gampeta, Stella</creatorcontrib><creatorcontrib>Gatselis, Nikolaos K.</creatorcontrib><creatorcontrib>Oikonomou, Katerina</creatorcontrib><creatorcontrib>Goulis, John</creatorcontrib><creatorcontrib>Manoussakis, Menelaos N.</creatorcontrib><creatorcontrib>Renaudineau, Yves</creatorcontrib><creatorcontrib>Bogdanos, Dimitrios P.</creatorcontrib><creatorcontrib>Dalekos, George N.</creatorcontrib><collection>Istex</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>Hyper Article en Ligne (HAL)</collection><jtitle>Liver international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zachou, Kalliopi</au><au>Gampeta, Stella</au><au>Gatselis, Nikolaos K.</au><au>Oikonomou, Katerina</au><au>Goulis, John</au><au>Manoussakis, Menelaos N.</au><au>Renaudineau, Yves</au><au>Bogdanos, Dimitrios P.</au><au>Dalekos, George N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-SLA/LP alone or in combination with anti-Ro52 and fine specificity of anti-Ro52 antibodies in patients with autoimmune hepatitis</atitle><jtitle>Liver international</jtitle><addtitle>Liver Int</addtitle><date>2015-02</date><risdate>2015</risdate><volume>35</volume><issue>2</issue><spage>660</spage><epage>672</epage><pages>660-672</pages><issn>1478-3223</issn><eissn>1478-3231</eissn><abstract>Background &amp; Aims Antibodies (Abs) to soluble liver antigen/liver pancreas (anti‐SLA/LP) are considered markers of worse prognosis and outcome in patients with autoimmune hepatitis (AIH) although this assumption has recently been attributed to their frequent co‐expression with Abs against Ro52 (anti‐Ro52). To assess the clinical significance of anti‐SLA/LP Abs alone or in combination with anti‐Ro52 in AIH patients and determine the immunodominant Ro52 epitopes according to the anti‐SLA/LP status. Methods Twenty‐three anti‐SLA/LP‐positive and 106 anti‐SLA/LP‐negative AIH patients were included. Anti‐SLA/LP were determined by ELISA using recombinant antigen, and confirmed by immunoblot using cytosolic rat liver fraction or HuH‐7 extract. Anti‐Ro52 Abs were determined by ELISA using recombinant antigen. Epitope mapping was assessed by ELISA using overlapping peptides covering the whole Ro52 protein in 26 AIH patients and 12 patients with Sjögren's syndrome. Results Anti‐SLA/LP positivity was not associated with the clinical, laboratory or histological characteristics of AIH patients. Treatment response, corticosteroid withdrawal, relapse after stopping treatment and outcome, were not associated with the presence of anti‐SLA/LP, anti‐Ro52 or double reactivity. Moreover, Ro52 epitope mapping revealed new epitopes unique for AIH and independent from anti‐SLA/LP positivity. Conclusions Neither anti‐SLA/LP nor anti‐Ro52 Abs or their combination could specify a distinct group of AIH patients in terms of clinical characteristics, treatment response and outcome. Further studies are needed to clarify whether the newly discovered immunodominant epitopes of Ro52 antigen which were associated specifically with AIH have any clinical or pathogenetic significance in AIH.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25113420</pmid><doi>10.1111/liv.12658</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-5098-5002</orcidid></addata></record>
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source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects anti-Ro52 antibodies
anti-SLA/LP antibodies
Autoantibodies - blood
Autoantigens - blood
Autoantigens - immunology
autoimmune hepatitis
Biomarkers - blood
Enzyme-Linked Immunosorbent Assay
Epitope Mapping
Greece
Hepatitis, Autoimmune - blood
Hepatitis, Autoimmune - classification
Hepatitis, Autoimmune - immunology
Humans
Immunology
Kaplan-Meier Estimate
Life Sciences
Mycophenolic Acid - analogs & derivatives
Oligonucleotides
Polymerase Chain Reaction
Ribonucleoproteins - blood
Ribonucleoproteins - immunology
Sjögren's syndrome
title Anti-SLA/LP alone or in combination with anti-Ro52 and fine specificity of anti-Ro52 antibodies in patients with autoimmune hepatitis
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