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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 | MBL binds to a range of clinically relevent microorganisms and promotes complement diposition显示文摘 | Neth O Dominic L Alister W | 2000 | Infect Immun2000，68，2： | 1 |
| 3 | A new distance between two bodies of evidence显示文摘 | Jousselme A L Dominic G Bosse E | 2001 | Information Fusion2001，2，2： | 1 |
| 4 | Evolution of the specific surface area and of crystal morphology of Arctic fresh snow during the ALERT 2000 显示文摘 | Cabanes A Legagneux L Domin F | 2002 | Atmos Environ2002，36，： | 1 |
| 5 | A new dis-tance between two bodies of evidence显示文摘 | JOUSSELME A L DOMINIC G BOSSE E | 2001 | Information Fu-sion2001，2，2： | 1 |
| 6 | A new distance between two bodies of evidence 显示文摘 | Jousselme A L Dominic G Bosse E | 2001 | Information Fusion2001，2，： | 1 |
| 7 | A new distance between two bodies of evidence显示文摘 | Jousselme A L Dominic G Bosse E | 2001 | Information Fusion2001，，2： | 1 |
| 8 | A new distance between two bodies of evidence 显示文摘 | Jousselme A L Dominic G Bosse E | 2001 | Information Fusion2001，2，2： | 1 |
| 9 | Al-free Sn-beta zeolite as a catalyst for the selective reduction of carbonyl compounds (Meerwein-Ponndorf-Verley reaction) 显示文摘 | CORMA A DOMINE M E NEMETH L | 2002 | J Am Chem Soc2002，124，13： | 1 |
| 10 | Plasminogen dependent activation of latent transforminggrowth factor beta by growing cultures of osteoblast-like cells显示文摘 | 4,Yee JA Yan L Domin JC | 1993 | J CellPhysiol1993，157，5： | 1 |
| 11 | A new distance between two bodies of evidence显示文摘 | Jousselme A L Dominic G Bosse E | 2001 | Information Fusion2001，2，2： | 1 |
| 12 | Assessing the effect of land use change on catchment runoff by combined use of statistical tests and hydrological modelling:Case studies from Zimbabwe显示文摘 | Jens Kristian LΦrup Jens Christian Refsgaard Dominic Mazvimavi | | 0，，3： | 1 |
| 13 | Emergence of fluoroquinolone resistance among multiply resistant strsins of Streptococcus peumoniae in Hong Kong 显示文摘 | Ho P L Que T L Dominic N C | 1999 | Antimicrobial Agents Chemother1999，43，5： | 1 |
| 14 | Primary structure ofneuromedin U from the rat显示文摘 | CONLON J M DOMIN J THIM L | 1988 | Journal of Neurochemistry1988，51，3： | 1 |
| 15 | and business practice:A conceptual model of a service-dominant orientation 显示文摘 | Karpen I O Bove L L Lukas LinMng strategic service- dominant logic BA | 2011 | Journal of Service Research2011，，： | 1 |
| 16 | A new distance between two bodies of evidence显示文摘 | Jousselme A L Dominic G Bosse E | 2001 | Information Fusion2001，2，2： | 1 |
| 17 | A new distance between two bodies evidence显示文摘 | Jousselme A L Dominic G bosse E | 2001 | Information Fusion2001，2，2： | 1 |
| 18 | Al-Free Sn-beta Zeolite as a Catalyst for the Selective Reduction of Carbonyl Compounds(Meerwein-ponndorf-Verley Reaction)显示文摘 | Corma A Domine M E Nemeth L | 2002 | J Am Chem Soc2002，124，13： | 1 |
| 19 | Synthesis and structure-activity relationship study of cytotoxic germanicane and lupane-type 3β-O-monodesmosidic saponins starting from betulin显示文摘 | DOMINIC T CHARLES G JEAN L | 2007 | Bioorganic & Medicinal Chemistry2007，15，： | 1 |
| 20 | Impa- cat of free-falling wedge with water:syn-chronized visual-ization, pressure and acceleration measurement 显示文摘 | Simon G L Dominic A H Stephen R Turnock | 2010 | Fluid Dynamics Research2010，42，3： | 1 |
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