Anti-TNF treatment blocks the induction of T cell-dependent humoral responses
Identifieur interne : 000425 ( Main/Exploration ); précédent : 000424; suivant : 000426Anti-TNF treatment blocks the induction of T cell-dependent humoral responses
Auteurs : Gabriela Franco Salinas [Pays-Bas] ; Leen De Rycke [Pays-Bas] ; Barbara Barendregt [Pays-Bas] ; Jacqueline E. Paramarta [Pays-Bas] ; Hulda Hreggvidstdottir [Pays-Bas] ; Tineke Cantaert [Pays-Bas, États-Unis] ; Mirjam Van Der Burg [Pays-Bas] ; Paul P. Tak [Pays-Bas, Royaume-Uni] ; Dominique Baeten [Pays-Bas]Source :
- Annals of the Rheumatic Diseases [ 0003-4967 ] ; 2013-06.
Abstract
Objective Experimental and human data suggest that tumour necrosis factor (TNF) blockade may affect B cell responses, in particular the induction of T cell-dependent (TD) humoral immunity. This study aimed to assess this hypothesis directly in patients with arthritis by analysing longitudinally the effect of TNF blockade on B cell activation and the maturation of humoral responses against TD and T cell-independent vaccines. Materials and methods Peripheral blood samples were obtained from 56 spondyloarthritis patients before and after treatment with either non-steroidal anti-inflammatory drug (NSAID) alone or TNF blockers and analysed for B cell activation, plasma cell differentiation, germinal centre versus extra-follicular B cell maturation, and somatic hypermutation. Vaccine responses to hepatitis B and Streptococcus pneumoniae were measured by ELISA. Results TNF blockade augmented B cell activation as reflected by the expression of early activation markers, CD40, and costimulatory molecules, without affecting differentiation towards plasmablasts. This was associated with a specific increase of the unswitched fraction of circulating memory B cells and a decreased level of somatic hypermutation in anti-TNF treated patients, indicating an impairment of the germinal centre-dependent B cell maturation. In agreement with these findings, TNF blockade profoundly suppressed the response to the TD vaccination against hepatitis B, whereas the T cell-independent response against pneumococcal polysaccharides was only modestly affected. Conclusions These data indicate that TNF blockade severely impedes the induction of primary TD humoral responses, probably by interfering with the germinal centre reaction.
Url:
DOI: 10.1136/annrheumdis-2011-201270
Affiliations:
- Pays-Bas, Royaume-Uni, États-Unis
- Connecticut, Hollande-Méridionale, Hollande-Septentrionale, Utrecht (province)
- Amsterdam, Rotterdam, Utrecht
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Paramarta</name></author><author><name sortKey="Hreggvidstdottir, Hulda" sort="Hreggvidstdottir, Hulda" uniqKey="Hreggvidstdottir H" first="Hulda" last="Hreggvidstdottir">Hulda Hreggvidstdottir</name></author><author><name sortKey="Cantaert, Tineke" sort="Cantaert, Tineke" uniqKey="Cantaert T" first="Tineke" last="Cantaert">Tineke Cantaert</name></author><author><name sortKey="Van Der Burg, Mirjam" sort="Van Der Burg, Mirjam" uniqKey="Van Der Burg M" first="Mirjam" last="Van Der Burg">Mirjam Van Der Burg</name></author><author><name sortKey="Tak, Paul P" sort="Tak, Paul P" uniqKey="Tak P" first="Paul P" last="Tak">Paul P. 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Paramarta</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Hreggvidstdottir, Hulda" sort="Hreggvidstdottir, Hulda" uniqKey="Hreggvidstdottir H" first="Hulda" last="Hreggvidstdottir">Hulda Hreggvidstdottir</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Cantaert, Tineke" sort="Cantaert, Tineke" uniqKey="Cantaert T" first="Tineke" last="Cantaert">Tineke Cantaert</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Van Der Burg, Mirjam" sort="Van Der Burg, Mirjam" uniqKey="Van Der Burg M" first="Mirjam" last="Van Der Burg">Mirjam Van Der Burg</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Immunology, Erasmus Medical Centre, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Tak, Paul P" sort="Tak, Paul P" uniqKey="Tak P" first="Paul P" last="Tak">Paul P. Tak</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Glaxo Smith Kline, Stevenage</wicri:regionArea><wicri:noRegion>Stevenage</wicri:noRegion></affiliation></author><author><name sortKey="Baeten, Dominique" sort="Baeten, Dominique" uniqKey="Baeten D" first="Dominique" last="Baeten">Dominique Baeten</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Clinical Immunology and Rheumatology, Academic Medical Centre/University of Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of the Rheumatic Diseases</title><title level="j" type="abbrev">Ann Rheum Dis</title><idno type="ISSN">0003-4967</idno><idno type="eISSN">1468-2060</idno><imprint><publisher>BMJ Publishing Group Ltd and European League Against Rheumatism</publisher><date type="published" when="2013-06">2013-06</date><biblScope unit="volume">72</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="1037">1037</biblScope></imprint><idno type="ISSN">0003-4967</idno></series><idno type="istex">E331ED3FB052C77F3F1E49A0F4E392076E712A1E</idno><idno type="DOI">10.1136/annrheumdis-2011-201270</idno><idno type="href">annrheumdis-72-1037.pdf</idno><idno type="ArticleID">annrheumdis-2011-201270</idno><idno type="PMID">22968102</idno><idno type="local">annrheumdis;72/6/1037</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0003-4967</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Objective Experimental and human data suggest that tumour necrosis factor (TNF) blockade may affect B cell responses, in particular the induction of T cell-dependent (TD) humoral immunity. This study aimed to assess this hypothesis directly in patients with arthritis by analysing longitudinally the effect of TNF blockade on B cell activation and the maturation of humoral responses against TD and T cell-independent vaccines. Materials and methods Peripheral blood samples were obtained from 56 spondyloarthritis patients before and after treatment with either non-steroidal anti-inflammatory drug (NSAID) alone or TNF blockers and analysed for B cell activation, plasma cell differentiation, germinal centre versus extra-follicular B cell maturation, and somatic hypermutation. Vaccine responses to hepatitis B and Streptococcus pneumoniae were measured by ELISA. Results TNF blockade augmented B cell activation as reflected by the expression of early activation markers, CD40, and costimulatory molecules, without affecting differentiation towards plasmablasts. This was associated with a specific increase of the unswitched fraction of circulating memory B cells and a decreased level of somatic hypermutation in anti-TNF treated patients, indicating an impairment of the germinal centre-dependent B cell maturation. In agreement with these findings, TNF blockade profoundly suppressed the response to the TD vaccination against hepatitis B, whereas the T cell-independent response against pneumococcal polysaccharides was only modestly affected. Conclusions These data indicate that TNF blockade severely impedes the induction of primary TD humoral responses, probably by interfering with the germinal centre reaction.</div></front></TEI><affiliations><list><country><li>Pays-Bas</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Connecticut</li><li>Hollande-Méridionale</li><li>Hollande-Septentrionale</li><li>Utrecht (province)</li></region><settlement><li>Amsterdam</li><li>Rotterdam</li><li>Utrecht</li></settlement></list><tree><country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Franco Salinas, Gabriela" sort="Franco Salinas, Gabriela" uniqKey="Franco Salinas G" first="Gabriela" last="Franco Salinas">Gabriela Franco Salinas</name></region><name sortKey="Baeten, Dominique" sort="Baeten, Dominique" uniqKey="Baeten D" first="Dominique" last="Baeten">Dominique Baeten</name><name sortKey="Barendregt, Barbara" sort="Barendregt, Barbara" uniqKey="Barendregt B" first="Barbara" last="Barendregt">Barbara Barendregt</name><name sortKey="Cantaert, Tineke" sort="Cantaert, Tineke" uniqKey="Cantaert T" first="Tineke" last="Cantaert">Tineke Cantaert</name><name sortKey="De Rycke, Leen" sort="De Rycke, Leen" uniqKey="De Rycke L" first="Leen" last="De Rycke">Leen De Rycke</name><name sortKey="De Rycke, Leen" sort="De Rycke, Leen" uniqKey="De Rycke L" first="Leen" last="De Rycke">Leen De Rycke</name><name sortKey="Hreggvidstdottir, Hulda" sort="Hreggvidstdottir, Hulda" uniqKey="Hreggvidstdottir H" first="Hulda" last="Hreggvidstdottir">Hulda Hreggvidstdottir</name><name sortKey="Paramarta, Jacqueline E" sort="Paramarta, Jacqueline E" uniqKey="Paramarta J" first="Jacqueline E" last="Paramarta">Jacqueline E. Paramarta</name><name sortKey="Tak, Paul P" sort="Tak, Paul P" uniqKey="Tak P" first="Paul P" last="Tak">Paul P. Tak</name><name sortKey="Van Der Burg, Mirjam" sort="Van Der Burg, Mirjam" uniqKey="Van Der Burg M" first="Mirjam" last="Van Der Burg">Mirjam Van Der Burg</name></country><country name="États-Unis"><region name="Connecticut"><name sortKey="Cantaert, Tineke" sort="Cantaert, Tineke" uniqKey="Cantaert T" first="Tineke" last="Cantaert">Tineke Cantaert</name></region></country><country name="Royaume-Uni"><noRegion><name sortKey="Tak, Paul P" sort="Tak, Paul P" uniqKey="Tak P" first="Paul P" last="Tak">Paul P. Tak</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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