Immunomodulation of RA Patients' PBMC with a Multiepitope Peptide Derived from Citrullinated Autoantigens
Identifieur interne : 001793 ( Main/Exploration ); précédent : 001792; suivant : 001794Immunomodulation of RA Patients' PBMC with a Multiepitope Peptide Derived from Citrullinated Autoantigens
Auteurs : Smadar Gertel [Israël] ; Gidi Karmon [Israël] ; Sivan Vainer [Israël] ; Ora Shovman [Israël] ; Martin Cornillet [France] ; Guy Serre [France] ; Yehuda Shoenfeld [Israël] ; Howard Amital [Israël]Source :
- Mediators of Inflammation [ 0962-9351 ] ; 2017.
Abstract
Citrullinated peptides are used for measuring anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). Accumulation of citrullinated proteins in the inflamed synovium suggests that they may be good targets for inducing peripheral tolerance. In view of the multiplicity of citrullinated autoantigens described as ACPA targets, we generated a multiepitope citrullinated peptide (Cit-ME) from the sequences of major citrullinated autoantigens: filaggrin,
Url:
DOI: 10.1155/2017/3916519
PubMed: 28751821
PubMed Central: 5497640
Affiliations:
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Autoantigens</title><author><name sortKey="Gertel, Smadar" sort="Gertel, Smadar" uniqKey="Gertel S" first="Smadar" last="Gertel">Smadar Gertel</name><affiliation wicri:level="1"><nlm:aff id="I1">Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan</wicri:regionArea><wicri:noRegion>5262100 Ramat-Gan</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv</wicri:regionArea><wicri:noRegion>6997801 Tel-Aviv</wicri:noRegion></affiliation></author><author><name sortKey="Karmon, Gidi" sort="Karmon, Gidi" uniqKey="Karmon G" first="Gidi" last="Karmon">Gidi Karmon</name><affiliation wicri:level="1"><nlm:aff id="I1">Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan</wicri:regionArea><wicri:noRegion>5262100 Ramat-Gan</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv</wicri:regionArea><wicri:noRegion>6997801 Tel-Aviv</wicri:noRegion></affiliation></author><author><name sortKey="Vainer, Sivan" sort="Vainer, Sivan" uniqKey="Vainer S" first="Sivan" last="Vainer">Sivan Vainer</name><affiliation wicri:level="1"><nlm:aff id="I1">Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan</wicri:regionArea><wicri:noRegion>5262100 Ramat-Gan</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv</wicri:regionArea><wicri:noRegion>6997801 Tel-Aviv</wicri:noRegion></affiliation></author><author><name sortKey="Shovman, Ora" sort="Shovman, Ora" uniqKey="Shovman O" first="Ora" last="Shovman">Ora Shovman</name><affiliation wicri:level="1"><nlm:aff id="I1">Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan</wicri:regionArea><wicri:noRegion>5262100 Ramat-Gan</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv</wicri:regionArea><wicri:noRegion>6997801 Tel-Aviv</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I3">Department of Internal Medicine B, Sheba Medical Center, 5262100 Tel Hashomer, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Department of Internal Medicine B, Sheba Medical Center, 5262100 Tel Hashomer</wicri:regionArea><wicri:noRegion>5262100 Tel Hashomer</wicri:noRegion></affiliation></author><author><name sortKey="Cornillet, Martin" sort="Cornillet, Martin" uniqKey="Cornillet M" first="Martin" last="Cornillet">Martin Cornillet</name><affiliation wicri:level="3"><nlm:aff id="I4">Unité Différenciation Epithéliale et Autoimmunité Rhumatoïde, Université de Toulouse-INSERM, Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Différenciation Epithéliale et Autoimmunité Rhumatoïde, Université de Toulouse-INSERM, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="I5">Laboratoire de Biologie Cellulaire et Cytologie, CHU de Toulouse, Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biologie Cellulaire et Cytologie, CHU de Toulouse, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Serre, Guy" sort="Serre, Guy" uniqKey="Serre G" first="Guy" last="Serre">Guy Serre</name><affiliation wicri:level="3"><nlm:aff id="I4">Unité Différenciation Epithéliale et Autoimmunité Rhumatoïde, Université de Toulouse-INSERM, Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Différenciation Epithéliale et Autoimmunité Rhumatoïde, Université de Toulouse-INSERM, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="I5">Laboratoire de Biologie Cellulaire et Cytologie, CHU de Toulouse, Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biologie Cellulaire et Cytologie, CHU de Toulouse, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Shoenfeld, Yehuda" sort="Shoenfeld, Yehuda" uniqKey="Shoenfeld Y" first="Yehuda" last="Shoenfeld">Yehuda Shoenfeld</name><affiliation wicri:level="1"><nlm:aff id="I1">Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan</wicri:regionArea><wicri:noRegion>5262100 Ramat-Gan</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I6">Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Tel Aviv University, 6997801 Tel Aviv, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Tel Aviv University, 6997801 Tel Aviv</wicri:regionArea><wicri:noRegion>6997801 Tel Aviv</wicri:noRegion></affiliation></author><author><name sortKey="Amital, Howard" sort="Amital, Howard" uniqKey="Amital H" first="Howard" last="Amital">Howard Amital</name><affiliation wicri:level="1"><nlm:aff id="I1">Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100 Ramat-Gan</wicri:regionArea><wicri:noRegion>5262100 Ramat-Gan</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Sackler Faculty of Medicine, Tel-Aviv University, 6997801 Tel-Aviv</wicri:regionArea><wicri:noRegion>6997801 Tel-Aviv</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I3">Department of Internal Medicine B, Sheba Medical Center, 5262100 Tel Hashomer, Israel</nlm:aff><country xml:lang="fr">Israël</country><wicri:regionArea>Department of Internal Medicine B, Sheba Medical Center, 5262100 Tel Hashomer</wicri:regionArea><wicri:noRegion>5262100 Tel Hashomer</wicri:noRegion></affiliation></author></analytic><series><title level="j">Mediators of Inflammation</title><idno type="ISSN">0962-9351</idno><idno type="eISSN">1466-1861</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Citrullinated peptides are used for measuring anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). Accumulation of citrullinated proteins in the inflamed synovium suggests that they may be good targets for inducing peripheral tolerance. In view of the multiplicity of citrullinated autoantigens described as ACPA targets, we generated a multiepitope citrullinated peptide (Cit-ME) from the sequences of major citrullinated autoantigens: filaggrin, <italic>β</italic>-fibrinogen, vimentin, and collagen type II. We assessed the ability of Cit-ME or the citrullinated <italic>β</italic>60-74 fibrinogen peptide (<italic>β</italic>60-74-Fib-Cit) which bears immunodominant citrullinated epitopes (i) to modify cytokine gene expression and (ii) to modulate Treg and Th17 subsets in PBMC derived from newly diagnosed untreated RA patients. RA patient's PBMC incubated with Cit-ME or <italic>β</italic>60-74-Fib-Cit, showed upregulation of TGF-<italic>β</italic> expression (16% and 8%, resp.), and increased CD4<sup>+</sup>Foxp3<sup>+</sup> Treg (22% and 19%, resp.). Both peptides were shown to downregulate the TNF-<italic>α</italic> and IL-1<italic>β</italic> expression; in addition, Cit-ME reduced CD3<sup>+</sup>IL17<sup>+</sup> T cells. We showed that citrullinated peptides can modulate the expression of anti- and proinflammatory cytokines in PBMC from RA patients as well as the proportions of Treg and Th17 cells. These results indicate that citrullinated peptides could be active in vivo and therefore might be used as immunoregulatory agents in RA patients.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Imboden, J B" uniqKey="Imboden J">J. B. Imboden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nielen, M M" uniqKey="Nielen M">M. M. Nielen</name></author><author><name sortKey="Van Schaardenburg, D" uniqKey="Van Schaardenburg D">D. van Schaardenburg</name></author><author><name sortKey="Reesink, H W" uniqKey="Reesink H">H. W. 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Ehrenstein</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>France</li><li>Israël</li></country><region><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li></region><settlement><li>Toulouse</li></settlement></list><tree><country name="Israël"><noRegion><name sortKey="Gertel, Smadar" sort="Gertel, Smadar" uniqKey="Gertel S" first="Smadar" last="Gertel">Smadar Gertel</name></noRegion><name sortKey="Amital, Howard" sort="Amital, Howard" uniqKey="Amital H" first="Howard" last="Amital">Howard Amital</name><name sortKey="Amital, Howard" sort="Amital, Howard" uniqKey="Amital H" first="Howard" last="Amital">Howard Amital</name><name sortKey="Amital, Howard" sort="Amital, Howard" uniqKey="Amital H" first="Howard" last="Amital">Howard Amital</name><name sortKey="Gertel, Smadar" sort="Gertel, Smadar" uniqKey="Gertel S" first="Smadar" last="Gertel">Smadar Gertel</name><name sortKey="Karmon, Gidi" sort="Karmon, Gidi" uniqKey="Karmon G" first="Gidi" last="Karmon">Gidi Karmon</name><name sortKey="Karmon, Gidi" sort="Karmon, Gidi" uniqKey="Karmon G" first="Gidi" last="Karmon">Gidi Karmon</name><name sortKey="Shoenfeld, Yehuda" sort="Shoenfeld, Yehuda" uniqKey="Shoenfeld Y" first="Yehuda" last="Shoenfeld">Yehuda Shoenfeld</name><name sortKey="Shoenfeld, Yehuda" sort="Shoenfeld, Yehuda" uniqKey="Shoenfeld Y" first="Yehuda" last="Shoenfeld">Yehuda Shoenfeld</name><name sortKey="Shovman, Ora" sort="Shovman, Ora" uniqKey="Shovman O" first="Ora" last="Shovman">Ora Shovman</name><name sortKey="Shovman, Ora" sort="Shovman, Ora" uniqKey="Shovman O" first="Ora" last="Shovman">Ora Shovman</name><name sortKey="Shovman, Ora" sort="Shovman, Ora" uniqKey="Shovman O" first="Ora" last="Shovman">Ora Shovman</name><name sortKey="Vainer, Sivan" sort="Vainer, Sivan" uniqKey="Vainer S" first="Sivan" last="Vainer">Sivan Vainer</name><name sortKey="Vainer, Sivan" sort="Vainer, Sivan" uniqKey="Vainer S" first="Sivan" last="Vainer">Sivan Vainer</name></country><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Cornillet, Martin" sort="Cornillet, Martin" uniqKey="Cornillet M" first="Martin" last="Cornillet">Martin Cornillet</name></region><name sortKey="Cornillet, Martin" sort="Cornillet, Martin" uniqKey="Cornillet M" first="Martin" last="Cornillet">Martin Cornillet</name><name sortKey="Serre, Guy" sort="Serre, Guy" uniqKey="Serre G" first="Guy" last="Serre">Guy Serre</name><name sortKey="Serre, Guy" sort="Serre, Guy" uniqKey="Serre G" first="Guy" last="Serre">Guy Serre</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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