Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy
Identifieur interne : 002060 ( Main/Exploration ); précédent : 002059; suivant : 002061Dysregulation 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
Affiliations:
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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><idno type="wicri:Area/Pmc/Checkpoint">000999</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000999</idno><idno type="wicri:Area/Ncbi/Merge">003F42</idno><idno type="wicri:Area/Ncbi/Curation">003F42</idno><idno type="wicri:Area/Ncbi/Checkpoint">003F42</idno><idno type="wicri:doubleKey">1007-9327:2016:Baird A:dysregulation:of:innate</idno><idno type="wicri:Area/Main/Merge">002059</idno><idno type="wicri:Area/Main/Curation">002060</idno><idno type="wicri:Area/Main/Exploration">002060</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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uniqKey="Hiki N">N Hiki</name></author><author><name sortKey="Ogawa, T" uniqKey="Ogawa T">T Ogawa</name></author><author><name sortKey="Mimura, Y" uniqKey="Mimura Y">Y Mimura</name></author><author><name sortKey="Kaminishi, M" uniqKey="Kaminishi M">M Kaminishi</name></author><author><name sortKey="Tanamoto, K" uniqKey="Tanamoto K">K Tanamoto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, J" uniqKey="Chang J">J Chang</name></author><author><name sortKey="Kunkel, Sl" uniqKey="Kunkel S">SL Kunkel</name></author><author><name sortKey="Chang, Ch" uniqKey="Chang C">CH Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ardesia, M" uniqKey="Ardesia M">M Ardesia</name></author><author><name sortKey="Villanacci, V" uniqKey="Villanacci V">V Villanacci</name></author><author><name sortKey="Fries, W" uniqKey="Fries W">W Fries</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Baird, Angela C" sort="Baird, Angela C" uniqKey="Baird A" first="Angela C" last="Baird">Angela C. Baird</name><name sortKey="Boyer, Julien" sort="Boyer, Julien" uniqKey="Boyer J" first="Julien" last="Boyer">Julien Boyer</name><name sortKey="Lawrance, Ian C" sort="Lawrance, Ian C" uniqKey="Lawrance I" first="Ian C" last="Lawrance">Ian C. Lawrance</name><name sortKey="Mallon, Dominic" sort="Mallon, Dominic" uniqKey="Mallon D" first="Dominic" last="Mallon">Dominic Mallon</name><name sortKey="Piche, Thierry" sort="Piche, Thierry" uniqKey="Piche T" first="Thierry" last="Piche">Thierry Piche</name><name sortKey="Prescott, Susan L" sort="Prescott, Susan L" uniqKey="Prescott S" first="Susan L" last="Prescott">Susan L. Prescott</name><name sortKey="Radford Smith, Graham" sort="Radford Smith, Graham" uniqKey="Radford Smith G" first="Graham" last="Radford-Smith">Graham Radford-Smith</name><name sortKey="Tulic, Meri K" sort="Tulic, Meri K" uniqKey="Tulic M" first="Meri K" last="Tulic">Meri K. Tulic</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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