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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 | Synthesis and photophysical properties of borondipyrromethene dyes bearing aryl substituents at the boron center显示文摘 | Goze C Ulrich G Mallon L J | | 0，，31： | 1 |
| 3 | High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged population显示文摘 | MALLON L BROMAN J E HETTA J | 2005 | Dia betes Care2005，28，11： | 1 |
| 4 | High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged population显示文摘 | Mallon L Broman JE Hetta J | 2005 | Diabetes Care2005，28，： | 1 |
| 5 | High incidence of diabetes in men with sleep complaints or short sleep duration 显示文摘 | Mallon L Broman JE Hetta J | 2005 | Diabetes Care2005，28，： | 1 |
| 6 | Sleep complaints predict coro- nary artery disease mortality in males: a 12-year follow-up study of a middle-aged Swedish population显示文摘 | Mallon L Broman J E Hetta J | 2002 | Journal of Internal Medicine2002，251，： | 1 |
| 7 | Estimation of impervi- ousness and specific curb length for forecasting stormwater quality and quantity显示文摘 | Graham P H Costello L S Mallon H J | 1974 | Journal of Water Pollution Control Federation1974，46，4： | 1 |
| 8 | High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year fol- low-up study of a middle-aged population 显示文摘 | Mallon L Broman JE Hetta J | 2005 | Diabetes Care2005，28，11： | 1 |
| 9 | Osteoclast-like giant cell tumor arising in the soft tissue of the breast: report of a case显示文摘 | Romics L Mallon EA Reid R | 2009 | Surg Today2009，39，1： | 1 |
| 10 | In vitro micropropagation and long-term conservation of the endangered moss Splachnum ampullaceum显示文摘 | GONZALEZ M L MALLON R REINOSO J | 2006 | Biol Plant2006，50，： | 1 |
| 11 | Prognostic impact of discrepant Ki67 and mitotic index on hormone receptor-positive, HER2-nega- tive breast carcinoma显示文摘 | Rossi L Laas E Mallon P | 2015 | Br J Cancer2015，113，7： | 1 |
| 12 | High incidence of diabetes in men with sleep complaints or short sleep duration:a 12-year follow-up study of a middle-aged population显示文摘 | Mallon L Broman JE Hetta J | | 0，，11： | 1 |
| 13 | From Bicycle Sharing System Movements to Users: A Typology of V61o'v Cyclists in Lyon Based on Large- scale Behavioural Dataset显示文摘 | Vogel M Hamon R Lozenguez G Merchez L Abry P Barnier J Borgnat P Flandrin P Mallon I Robardet C | 2014 | Journal of Transport Geography2014，41，： | 1 |
| 14 | High incidence of diabetes in men with sleep complaints or short sleep duration: a 12 -year follow -up study of a middle - aged population 显示文摘 | Mallon L Broman JE Hetta J | 2005 | Diabetes Care2005，28，11： | 1 |
| 15 | A near-IR emitting Bodipy-based dye fitted with ancillary light harvesting units显示文摘 | Harriman A Mallon L J Goeb S B | | 0，，： | 1 |
| 16 | High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged population 显示文摘 | Mallon L Broman JE Hetta J | 2005 | Diabetes Care2005，28，11： | 1 |
| 17 | Relationship between insomnia,depression,and mortality:a 12-years follow-up of older adults in the community显示文摘 | Mallon L Broman JE Hetta L | 2000 | Int Psychogeriatr2000，12，3： | 1 |
| 18 | High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged populatio 显示文摘 | Mallon L Broman JE Hetta J | 2005 | Diabetes Care2005，28，11： | 1 |
| 19 | Cost benefit of influenza vaccination in healthy, working adults: an economic analysis based on the results of an influenza virus vaccine显示文摘 | Nichol K L Mallon K P Mendelman P M | 2002 | Vaccine2002，21，22： | 1 |
| 20 | High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged population 显示文摘 | Mallon L Broman JE Hetta J | 2005 | Diabetes Care2005，28，11： | 1 |
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