Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy
Identifieur interne : 002B95 ( Pmc/Curation ); précédent : 002B94; suivant : 002B96Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy
Auteurs : Angela C. Baird ; Dominic Mallon ; Graham Radford-Smith ; Julien Boyer ; Thierry Piche ; Susan L. Prescott ; Ian C. Lawrance ; Meri K. TulicSource :
- World Journal of Gastroenterology [ 1007-9327 ] ; 2016.
Abstract
To study the innate immune function in ulcerative colitis (UC) patients who fail to respond to anti-tumor necrosis factor (TNF) therapy.
Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR stimulation was assessed in UC “responders” (
Prior to anti-TNF therapy, responders and non-responders had similar level of disease severity and activity. PBMC’s ability to respond to TLR stimulation was not affected by TNF therapy, patient’s severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders (
Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy.
Url:
DOI: 10.3748/wjg.v22.i41.9104
PubMed: 27895398
PubMed Central: 5107592
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy</title><author><name sortKey="Baird, Angela C" sort="Baird, Angela C" uniqKey="Baird A" first="Angela C" last="Baird">Angela C. Baird</name></author><author><name sortKey="Mallon, Dominic" sort="Mallon, Dominic" uniqKey="Mallon D" first="Dominic" last="Mallon">Dominic Mallon</name></author><author><name sortKey="Radford Smith, Graham" sort="Radford Smith, Graham" uniqKey="Radford Smith G" first="Graham" last="Radford-Smith">Graham Radford-Smith</name></author><author><name sortKey="Boyer, Julien" sort="Boyer, Julien" uniqKey="Boyer J" first="Julien" last="Boyer">Julien Boyer</name></author><author><name sortKey="Piche, Thierry" sort="Piche, Thierry" uniqKey="Piche T" first="Thierry" last="Piche">Thierry Piche</name></author><author><name sortKey="Prescott, Susan L" sort="Prescott, Susan L" uniqKey="Prescott S" first="Susan L" last="Prescott">Susan L. Prescott</name></author><author><name sortKey="Lawrance, Ian C" sort="Lawrance, Ian C" uniqKey="Lawrance I" first="Ian C" last="Lawrance">Ian C. Lawrance</name></author><author><name sortKey="Tulic, Meri K" sort="Tulic, Meri K" uniqKey="Tulic M" first="Meri K" last="Tulic">Meri K. Tulic</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27895398</idno><idno type="pmc">5107592</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107592</idno><idno type="RBID">PMC:5107592</idno><idno type="doi">10.3748/wjg.v22.i41.9104</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">002D45</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002D45</idno><idno type="wicri:Area/Pmc/Curation">002B95</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002B95</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy</title><author><name sortKey="Baird, Angela C" sort="Baird, Angela C" uniqKey="Baird A" first="Angela C" last="Baird">Angela C. Baird</name></author><author><name sortKey="Mallon, Dominic" sort="Mallon, Dominic" uniqKey="Mallon D" first="Dominic" last="Mallon">Dominic Mallon</name></author><author><name sortKey="Radford Smith, Graham" sort="Radford Smith, Graham" uniqKey="Radford Smith G" first="Graham" last="Radford-Smith">Graham Radford-Smith</name></author><author><name sortKey="Boyer, Julien" sort="Boyer, Julien" uniqKey="Boyer J" first="Julien" last="Boyer">Julien Boyer</name></author><author><name sortKey="Piche, Thierry" sort="Piche, Thierry" uniqKey="Piche T" first="Thierry" last="Piche">Thierry Piche</name></author><author><name sortKey="Prescott, Susan L" sort="Prescott, Susan L" uniqKey="Prescott S" first="Susan L" last="Prescott">Susan L. Prescott</name></author><author><name sortKey="Lawrance, Ian C" sort="Lawrance, Ian C" uniqKey="Lawrance I" first="Ian C" last="Lawrance">Ian C. Lawrance</name></author><author><name sortKey="Tulic, Meri K" sort="Tulic, Meri K" uniqKey="Tulic M" first="Meri K" last="Tulic">Meri K. Tulic</name></author></analytic><series><title level="j">World Journal of Gastroenterology</title><idno type="ISSN">1007-9327</idno><idno type="eISSN">2219-2840</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>AIM</title><p>To study the innate immune function in ulcerative colitis (UC) patients who fail to respond to anti-tumor necrosis factor (TNF) therapy.</p></sec><sec><title>METHODS</title><p>Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR stimulation was assessed in UC “responders” (<italic>n</italic> = 12) and “non-responders” (<italic>n</italic> = 12) and compared to healthy controls (<italic>n</italic> = 12). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory (TNF, IL-1β, IL-6), immuno-regulatory (IL-10), Th1 (IL-12, IFNγ) and Th2 (IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.</p></sec><sec><title>RESULTS</title><p>Prior to anti-TNF therapy, responders and non-responders had similar level of disease severity and activity. PBMC’s ability to respond to TLR stimulation was not affected by TNF therapy, patient’s severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders (<italic>P</italic> < 0.05). Following TLR stimulation, non-responders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls (<italic>P</italic> < 0.01) and diminished TNF (<italic>P</italic> < 0.001) and IL-1β (<italic>P</italic> < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells (pDCs) (<italic>P</italic> < 0.01) but increased number of CD4+ regulatory T cells (Tregs) (<italic>P</italic> = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2, -4 and -7 activation (<italic>P</italic> < 0.001).</p></sec><sec><title>CONCLUSION</title><p>Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. 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article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">World J Gastroenterol</journal-id><journal-id journal-id-type="iso-abbrev">World J. Gastroenterol</journal-id><journal-id journal-id-type="publisher-id">WJG</journal-id><journal-title-group><journal-title>World Journal of Gastroenterology</journal-title></journal-title-group><issn pub-type="ppub">1007-9327</issn><issn pub-type="epub">2219-2840</issn><publisher><publisher-name>Baishideng Publishing Group Inc</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27895398</article-id><article-id pub-id-type="pmc">5107592</article-id><article-id pub-id-type="other">jWJG.v22.i41.pg9104</article-id><article-id pub-id-type="doi">10.3748/wjg.v22.i41.9104</article-id><article-categories><subj-group subj-group-type="heading"><subject>Basic Study</subject></subj-group></article-categories><title-group><article-title>Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Baird</surname><given-names>Angela C</given-names></name></contrib><contrib contrib-type="author"><name><surname>Mallon</surname><given-names>Dominic</given-names></name></contrib><contrib contrib-type="author"><name><surname>Radford-Smith</surname><given-names>Graham</given-names></name></contrib><contrib contrib-type="author"><name><surname>Boyer</surname><given-names>Julien</given-names></name></contrib><contrib contrib-type="author"><name><surname>Piche</surname><given-names>Thierry</given-names></name></contrib><contrib contrib-type="author"><name><surname>Prescott</surname><given-names>Susan L</given-names></name></contrib><contrib contrib-type="author"><name><surname>Lawrance</surname><given-names>Ian C</given-names></name></contrib><contrib contrib-type="author"><name><surname>Tulic</surname><given-names>Meri K</given-names></name></contrib><aff>Angela C Baird, Ian C Lawrance, Faculty of Medicine and Dentistry, School of Medicine and Pharmacology, University of Western Australia, Perth, WA 6009, Australia</aff><aff>Dominic Mallon, Department of Immunology, Fremantle Hospital, Perth, WA 6160, Australia</aff><aff>Graham Radford-Smith, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, 4006, Australia</aff><aff>Julien Boyer, Thierry Piche, Meri K Tulic, University of Nice Sophia-Antipolis, EA6302, 06202 Nice, France</aff><aff>Julien Boyer, Thierry Piche, Department of Gastroenterology and Nutrition, l’Archet Hospital 2, 06202 Nice, France</aff><aff>Susan L Prescott, School of Paediatrics and Child Health, University of Western Australia, Subiaco, WA 6008, Australia</aff><aff>Susan L Prescott, Meri K Tulic, International Inflammation network (in-FLAME) of the World Universities Network, University of Western Australia, Subiaco, WA 6008, Australia</aff><aff>Ian C Lawrance, Centre for Inflammatory Bowel Diseases, St John of God Subiaco Hospital, Perth, WA 6009, Australia</aff><aff>Meri K Tulic, Mediterranean Center for Molecular Medicine (C3M)-INSERM U1065, Team 12, 06204 Nice, France</aff></contrib-group><author-notes><fn><p>Author contributions: Baird AC and Tulic MK were involved in data acquisition, analysis, interpretation of the data and writing of the manuscript; Baird AC, Mallon D, Radford-Smith G, Lawrance IC and Tulic MK were involved in study design; Prescott SL provided protocols and provision of laboratory space for some experiments; Boyer J, Piche T and Lawrance IC gave invaluable intellectual input into the study and clinical direction; Lawrance IC and Tulic MK proposed the original hypothesis of this study and approved the final version of this manuscript.</p><p>Correspondence to: Meri K Tulic, PhD, INSERM, CR1, Professor, Mediterranean Center for Molecular Medicine (C3M)-INSERM U1065, Team 12, Batiment Archimed, 151 route Saint-Antoine de Ginestiere, 06204 Nice, France. <email>meri.tulic@unice.fr</email></p><p>Telephone: +33-4-89064326 Fax: +33-4-89064221</p></fn></author-notes><pub-date pub-type="ppub"><day>7</day><month>11</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>7</day><month>11</month><year>2016</year></pub-date><volume>22</volume><issue>41</issue><fpage>9104</fpage><lpage>9116</lpage><history><date date-type="received"><day>8</day><month>7</month><year>2016</year></date><date date-type="rev-recd"><day>25</day><month>8</month><year>2016</year></date><date date-type="accepted"><day>28</day><month>9</month><year>2016</year></date></history><permissions><copyright-statement>©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.</copyright-statement><copyright-year>2016</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/"><license-p>This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.</license-p></license></permissions><abstract><sec><title>AIM</title><p>To study the innate immune function in ulcerative colitis (UC) patients who fail to respond to anti-tumor necrosis factor (TNF) therapy.</p></sec><sec><title>METHODS</title><p>Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR stimulation was assessed in UC “responders” (<italic>n</italic> = 12) and “non-responders” (<italic>n</italic> = 12) and compared to healthy controls (<italic>n</italic> = 12). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory (TNF, IL-1β, IL-6), immuno-regulatory (IL-10), Th1 (IL-12, IFNγ) and Th2 (IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.</p></sec><sec><title>RESULTS</title><p>Prior to anti-TNF therapy, responders and non-responders had similar level of disease severity and activity. PBMC’s ability to respond to TLR stimulation was not affected by TNF therapy, patient’s severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders (<italic>P</italic> < 0.05). Following TLR stimulation, non-responders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls (<italic>P</italic> < 0.01) and diminished TNF (<italic>P</italic> < 0.001) and IL-1β (<italic>P</italic> < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells (pDCs) (<italic>P</italic> < 0.01) but increased number of CD4+ regulatory T cells (Tregs) (<italic>P</italic> = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2, -4 and -7 activation (<italic>P</italic> < 0.001).</p></sec><sec><title>CONCLUSION</title><p>Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy.</p></sec></abstract><kwd-group><kwd>Ulcerative colitis</kwd><kwd>Innate immunity</kwd><kwd>Anti-tumor necrosis factor therapy</kwd><kwd>Toll-like receptor</kwd><kwd>IRAK4</kwd><kwd>Inflammatory bowel disease</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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