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| 1 | Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy显示文摘AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS 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'(n = 12) and 'non-responders'(n = 12) and compared to healthy controls(n = 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.RESULTS Prior to anti-TNF therapy, responders and nonresponders 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(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION 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. | Angela C Baird Dominic Mallon Graham Radford-Smith Julien Boyer Thierry Piche Susan L Prescott Ian C Lawrance Meri K Tulic | 2016 | World Journal of Gastroenterology2016，22，41： | 10 |
| 2 | Modulation of Bcl-2 protein levels by an intracellular anti-Bcl-2 single chain 显示文摘 | Grim J Rancourt C | 1998 | Cancer Res1998，58，10： | 1 |
| 3 | PCR mapping of integrons reveals several novel combinations of resistance genes显示文摘 | Levesque C Piche L Larose C | 1995 | Antimierob Agents Chemother1995，39，1： | 1 |
| 4 | Long isotropic buffer rods显示文摘 | Piche L Bussiere J F | 1990 | Acoustical Society of America1990，88，1： | 1 |
| 5 | Miniperp method for isolation of DNA form plants with a high content of polyphenolics显示文摘 | PICH C SCHUBERT I | 1993 | Nucleic Acids Research1993，21，14： | 1 |
| 6 | PCR mapping of integrons reveals several novel combinations of resistance genes显示文摘 | Leveoqoue C Piche L Larose | 1995 | Antimi- crob AgentsChemother1995，39，1： | 1 |
| 7 | Distribution of the messenger RNA for the smal conductance calciumactivated potassium channel SK3 in the adult rat brain and correlation with immunoreactivity显示文摘 | Tacconi S Carletti R Bunnemann B Plumpton C Merlo Pich E Terstappen GC | 2001 | Neuroscience2001，102，1： | 1 |
| 8 | Influence of high shear dispersion on the production of cellulose nanofibers by u显示文摘 | LORANGER E PICH A O DANEAULT C | 2012 | Nanoma terials2012，2，3： | 1 |
| 9 | Inhibitor sensitivity of respiratory complex Ⅰ in human platelets : a possible biomarker of ageing 显示文摘 | Merlo Pich M Bovina C Formiggini G | 1996 | FEBS Lett1996，380，12： | 1 |
| 10 | A multiplex PCR assay to characterize Potato virus Y isolates and identify strain mixtures显示文摘 | Loranzen J H Piche L M Gudmestad N C | 2006 | Plant Disease2006，，90： | 1 |
| 11 | In vivo effects in melanoma of ROCK inhibition-induced fasl overexpression 显示文摘 | Teiti I Florie B Pich C | 2015 | Front Oneol2015，145，5： | 1 |
| 12 | PCR mapping of integrons reveals several novel combinations of resistance genes 显示文摘 | Levesque C Piche L Larose C | 1995 | Antimi- crobial Agents and Chemotherapy1995，39，1： | 1 |
| 13 | Schubert method for isolation of DNA form plants with a high content of polyphenolies显示文摘 | Pich C | 1993 | Nucleic Research1993，21，14： | 1 |
| 14 | PCR mapping ot integrons reveals several novel combinations of resistance genes显示文摘 | Levesque C Piche L Larose C | | 0，，： | 1 |
| 15 | PCR mapping of integrons reveals several novel combinations of resistance genes显示文摘 | Levesque C Piche L Larose C | 1995 | Antimicrob Agents Chemother1995，39，1： | 1 |
| 16 | PCR mapping of integrons reveals several novel combinations of resistance genes显示文摘 | Levesque C Piche L Larose C | 1995 | Antimicrob Agents Chemother1995，39，1： | 1 |
| 17 | PCR mapping of integrons reveals several novel combinations of resistance genes 显示文摘 | Levesque C Piche L Larose C | 1995 | Antimicrob Agents Chemother1995，39，1： | 1 |
| 18 | Centrality estimation in large networks显示文摘 | Brandes U Pich C | 2007 | International Journal of Bifurcation and Chaos2007，17，7： | 1 |
| 19 | Effect of the F129L mutation in Alternaria solani on fungicides affecting mitochondrial respiration显示文摘 | PASCHE J S PICHE L M GUDMESTAD N C | 2005 | Plant Disease2005，89，3： | 1 |
| 20 | Circulating oxidized LDL is associated with parameters of the metabolic syndrome in postmenopausal women显示文摘 | Lapointe A Couillard C Piche ME | 2007 | Atherosclerosis2007，191，： | 1 |
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