SPRi-Based Strategy to Identify Specific Biomarkers in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Autoimmune Hepatitis
Identifieur interne : 001F13 ( Main/Curation ); précédent : 001F12; suivant : 001F14SPRi-Based Strategy to Identify Specific Biomarkers in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Autoimmune Hepatitis
Auteurs : Elvire Beleoken [France] ; Hervé Leh [France] ; Armelle Arnoux [France] ; Béatrice Ducot [France] ; Claude Nogues [France] ; Eleonora De Martin [France] ; Catherine Johanet [France] ; Didier Samuel [France] ; Mohammad Zahid Mustafa [France] ; Jean-Charles Duclos-Vallée [France] ; Malcolm Buckle [France] ; Eric Ballot [France]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Descripteurs français
- KwdFr :
- Anticorps antinucléaires (métabolisme), Humains, Hépatite auto-immune (métabolisme), Immunotransfert, Lupus érythémateux disséminé (métabolisme), Marqueurs biologiques (métabolisme), Peptides (métabolisme), Polyarthrite rhumatoïde (métabolisme), Ribonucléoprotéine nucléaire hétérogène du groupe A-B (métabolisme), Résonance plasmonique de surface (), Statistique non paramétrique, Technique d'immunofluorescence indirecte, Électrophorèse sur gel de polyacrylamide.
- MESH :
- métabolisme : Anticorps antinucléaires, Hépatite auto-immune, Lupus érythémateux disséminé, Marqueurs biologiques, Peptides, Polyarthrite rhumatoïde, Ribonucléoprotéine nucléaire hétérogène du groupe A-B.
- Humains, Immunotransfert, Résonance plasmonique de surface, Statistique non paramétrique, Technique d'immunofluorescence indirecte, Électrophorèse sur gel de polyacrylamide.
English descriptors
- KwdEn :
- Antibodies, Antinuclear (metabolism), Arthritis, Rheumatoid (metabolism), Biomarkers (metabolism), Electrophoresis, Polyacrylamide Gel, Fluorescent Antibody Technique, Indirect, Hepatitis, Autoimmune (metabolism), Heterogeneous-Nuclear Ribonucleoprotein Group A-B (metabolism), Humans, Immunoblotting, Lupus Erythematosus, Systemic (metabolism), Peptides (metabolism), Statistics, Nonparametric, Surface Plasmon Resonance (methods).
- MESH :
- chemical , metabolism : Antibodies, Antinuclear, Biomarkers, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Peptides.
- metabolism : Arthritis, Rheumatoid, Hepatitis, Autoimmune, Lupus Erythematosus, Systemic.
- methods : Surface Plasmon Resonance.
- Electrophoresis, Polyacrylamide Gel, Fluorescent Antibody Technique, Indirect, Humans, Immunoblotting, Statistics, Nonparametric.
Abstract
Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is a target for antinuclear autoantibodies in systemic Lupus erythematosus (SLE), rheumatoid arthritis (RA), and autoimmune hepatitis (AIH).
To monitor molecular interactions between peptides spanning the entire sequence of hnRNP A2/B1 and sera from patients and healthy controls.
Sera from 8 patients from each pathology and controls were passed across a surface plasmon resonance Imagery (SPRi) surface containing 39 overlapping peptides of 17 mers covering the human hnRNP B1. Interactions involving the immobilised peptides were followed in real time and dissociation rate constants koff for each interaction were calculated.
Several significant interactions were observed: i) high stability (lower koff values) between P55-70 and the AIH sera compared to controls (p= 0.003); ii) lower stability (higher koff values) between P118-133 and P262-277 and SLE sera, P145-160 and RA sera compared to controls (p=0.006, p=0.002, p=0.007). The binding curves and koff values observed after the formation of complexes with anti-IgM and anti-IgG antibodies and after nuclease treatment of the serum indicate that i) IgM isotypes are prevalent and ii) nucleic acids participate in the interaction between anti-hnRNAP B1 and P55-70 and also between controls and the peptides studied.
These results indicate that P55-70 of hnRNP B1 is a potential biomarker for AIH in immunological tests and suggest the role of circulating nucleic acids, (eg miRNA), present or absent according to the autoimmune disorders and involved in antigen-antibody stability.
Url:
DOI: 10.1371/journal.pone.0084600
PubMed: 24376828
PubMed Central: 3869893
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PMC:3869893Le document en format XML
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<author><name sortKey="Beleoken, Elvire" sort="Beleoken, Elvire" uniqKey="Beleoken E" first="Elvire" last="Beleoken">Elvire Beleoken</name>
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<author><name sortKey="Nogues, Claude" sort="Nogues, Claude" uniqKey="Nogues C" first="Claude" last="Nogues">Claude Nogues</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Laboratoire de Biologie et de Pharmacologie Appliquée, ENS Cachan - CNRS, Cachan, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
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</affiliation>
</author>
<author><name sortKey="De Martin, Eleonora" sort="De Martin, Eleonora" uniqKey="De Martin E" first="Eleonora" last="De Martin">Eleonora De Martin</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Research Unit 785, Inserm, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Research Unit 785, Inserm, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Faculte de Medecine, University Paris-Sud, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Faculte de Medecine, University Paris-Sud, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff6"><addr-line>Laboratoire Immunologie, AP-HP Hopital Saint-Antoine, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire Immunologie, AP-HP Hopital Saint-Antoine, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Johanet, Catherine" sort="Johanet, Catherine" uniqKey="Johanet C" first="Catherine" last="Johanet">Catherine Johanet</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Research Unit 785, Inserm, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Research Unit 785, Inserm, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff6"><addr-line>Laboratoire Immunologie, AP-HP Hopital Saint-Antoine, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire Immunologie, AP-HP Hopital Saint-Antoine, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="aff7"><addr-line>Faculté de Médecine UFR 967, Université Pierre et Marie Curie, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Faculté de Médecine UFR 967, Université Pierre et Marie Curie, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
<orgName type="university">Université Pierre-et-Marie-Curie</orgName>
</affiliation>
</author>
<author><name sortKey="Samuel, Didier" sort="Samuel, Didier" uniqKey="Samuel D" first="Didier" last="Samuel">Didier Samuel</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Research Unit 785, Inserm, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Research Unit 785, Inserm, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Faculte de Medecine, University Paris-Sud, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Faculte de Medecine, University Paris-Sud, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mustafa, Mohammad Zahid" sort="Mustafa, Mohammad Zahid" uniqKey="Mustafa M" first="Mohammad Zahid" last="Mustafa">Mohammad Zahid Mustafa</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Research Unit 785, Inserm, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Research Unit 785, Inserm, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Faculte de Medecine, University Paris-Sud, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Faculte de Medecine, University Paris-Sud, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Duclos Vallee, Jean Charles" sort="Duclos Vallee, Jean Charles" uniqKey="Duclos Vallee J" first="Jean-Charles" last="Duclos-Vallée">Jean-Charles Duclos-Vallée</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Research Unit 785, Inserm, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Research Unit 785, Inserm, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Faculte de Medecine, University Paris-Sud, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Faculte de Medecine, University Paris-Sud, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff8"><addr-line>Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre Hépato-Biliaire, AP-HP Hôpital Paul Brousse, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Buckle, Malcolm" sort="Buckle, Malcolm" uniqKey="Buckle M" first="Malcolm" last="Buckle">Malcolm Buckle</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Laboratoire de Biologie et de Pharmacologie Appliquée, ENS Cachan - CNRS, Cachan, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire de Biologie et de Pharmacologie Appliquée, ENS Cachan - CNRS, Cachan</wicri:regionArea>
<wicri:noRegion>Cachan</wicri:noRegion>
<wicri:noRegion>Cachan</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ballot, Eric" sort="Ballot, Eric" uniqKey="Ballot E" first="Eric" last="Ballot">Eric Ballot</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Research Unit 785, Inserm, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Research Unit 785, Inserm, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Faculte de Medecine, University Paris-Sud, Villejuif, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Faculte de Medecine, University Paris-Sud, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="aff6"><addr-line>Laboratoire Immunologie, AP-HP Hopital Saint-Antoine, Paris, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire Immunologie, AP-HP Hopital Saint-Antoine, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2013">2013</date>
</imprint>
</series>
</biblStruct>
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</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antibodies, Antinuclear (metabolism)</term>
<term>Arthritis, Rheumatoid (metabolism)</term>
<term>Biomarkers (metabolism)</term>
<term>Electrophoresis, Polyacrylamide Gel</term>
<term>Fluorescent Antibody Technique, Indirect</term>
<term>Hepatitis, Autoimmune (metabolism)</term>
<term>Heterogeneous-Nuclear Ribonucleoprotein Group A-B (metabolism)</term>
<term>Humans</term>
<term>Immunoblotting</term>
<term>Lupus Erythematosus, Systemic (metabolism)</term>
<term>Peptides (metabolism)</term>
<term>Statistics, Nonparametric</term>
<term>Surface Plasmon Resonance (methods)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Anticorps antinucléaires (métabolisme)</term>
<term>Humains</term>
<term>Hépatite auto-immune (métabolisme)</term>
<term>Immunotransfert</term>
<term>Lupus érythémateux disséminé (métabolisme)</term>
<term>Marqueurs biologiques (métabolisme)</term>
<term>Peptides (métabolisme)</term>
<term>Polyarthrite rhumatoïde (métabolisme)</term>
<term>Ribonucléoprotéine nucléaire hétérogène du groupe A-B (métabolisme)</term>
<term>Résonance plasmonique de surface ()</term>
<term>Statistique non paramétrique</term>
<term>Technique d'immunofluorescence indirecte</term>
<term>Électrophorèse sur gel de polyacrylamide</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antibodies, Antinuclear</term>
<term>Biomarkers</term>
<term>Heterogeneous-Nuclear Ribonucleoprotein Group A-B</term>
<term>Peptides</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Arthritis, Rheumatoid</term>
<term>Hepatitis, Autoimmune</term>
<term>Lupus Erythematosus, Systemic</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Surface Plasmon Resonance</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Anticorps antinucléaires</term>
<term>Hépatite auto-immune</term>
<term>Lupus érythémateux disséminé</term>
<term>Marqueurs biologiques</term>
<term>Peptides</term>
<term>Polyarthrite rhumatoïde</term>
<term>Ribonucléoprotéine nucléaire hétérogène du groupe A-B</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Electrophoresis, Polyacrylamide Gel</term>
<term>Fluorescent Antibody Technique, Indirect</term>
<term>Humans</term>
<term>Immunoblotting</term>
<term>Statistics, Nonparametric</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Humains</term>
<term>Immunotransfert</term>
<term>Résonance plasmonique de surface</term>
<term>Statistique non paramétrique</term>
<term>Technique d'immunofluorescence indirecte</term>
<term>Électrophorèse sur gel de polyacrylamide</term>
</keywords>
</textClass>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><sec sec-type="headed"><title>Background</title>
<p>Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is a target for antinuclear autoantibodies in systemic Lupus erythematosus (SLE), rheumatoid arthritis (RA), and autoimmune hepatitis (AIH). </p>
</sec>
<sec sec-type="headed"><title>Aim</title>
<p>To monitor molecular interactions between peptides spanning the entire sequence of hnRNP A2/B1 and sera from patients and healthy controls.</p>
</sec>
<sec sec-type="headed"><title>Methods</title>
<p>Sera from 8 patients from each pathology and controls were passed across a surface plasmon resonance Imagery (SPRi) surface containing 39 overlapping peptides of 17 mers covering the human hnRNP B1. Interactions involving the immobilised peptides were followed in real time and dissociation rate constants k<sub>off</sub>
for each interaction were calculated.</p>
</sec>
<sec sec-type="headed"><title>Results</title>
<p>Several significant interactions were observed: i) high stability (lower k<sub>off</sub>
values) between P<sub>55-70</sub>
and the AIH sera compared to controls (p= 0.003); ii) lower stability (higher k<sub>off</sub>
values) between P<sub>118-133</sub>
and P<sub>262-277</sub>
and SLE sera, P<sub>145-160</sub>
and RA sera compared to controls (p=0.006, p=0.002, p=0.007). The binding curves and k<sub>off</sub>
values observed after the formation of complexes with anti-IgM and anti-IgG antibodies and after nuclease treatment of the serum indicate that i) IgM isotypes are prevalent and ii) nucleic acids participate in the interaction between anti-hnRNAP B1 and P<sub>55-70</sub>
and also between controls and the peptides studied.</p>
</sec>
<sec sec-type="headed"><title>Conclusions</title>
<p>These results indicate that P<sub>55-70</sub>
of hnRNP B1 is a potential biomarker for AIH in immunological tests and suggest the role of circulating nucleic acids, (eg miRNA), present or absent according to the autoimmune disorders and involved in antigen-antibody stability.</p>
</sec>
</div>
</front>
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