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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 | Prognostic value of nutritional status in chronic obstructive pulmonary disease显示文摘 | Landbo C Prescott E Lange P | 1999 | Am J Respir Crit Care Med1999，160，6： | 2 |
| 3 | Prognostic value of nutritional status in chronic obstructive pulmonary disease显示文摘 | Landbo C Prescott E Lange P | 1999 | Am J Respir Crit Care Med1999，160，6： | 1 |
| 4 | Prognostic value of nutritional status in chronic obstructive pulmonary disease显示文摘 | Landbo C Prescott E Lange P | 1999 | Am J Respir Crit Care Med1999，160，： | 1 |
| 5 | The equity premium:A puzzle显示文摘 | Mehra R Prescott E C | 1985 | Journal of monetary Economics1985，15，2： | 1 |
| 6 | Time to Build and Aggregate Fluctuations显示文摘 | Kyland F E Prescott E C | 1982 | Econometrica1982，，50： | 1 |
| 7 | Innovation in the multinational firm with globally dispersed R&D: Technological knowledge utilization and accumulation显示文摘 | Prescott C E | 1999 | Journal of High Technology Management Research1999，10，2： | 1 |
| 8 | Prognostic valne of nutritional status in chronic obstructive pulmonary disease显示文摘 | Landbo C Prescott E Lange P | 1999 | Am J Respir Crit Care Med1999，160，6： | 1 |
| 9 | Competing explanations for knowledge exchange: Technology sharing within the globally dispersed R&D of the multinational enterprise 显示文摘 | PRESCOTT C ENSIGN LOUIS HEBERT | 2009 | Journal of High Technology Management Research2009，，20： | 1 |
| 10 | Malthus to Solow 显示文摘 | HANSEN GARY D EDWARD C PRESCOTt | 2002 | American Economic Review2002，92，： | 1 |
| 11 | Financiallntermediary-Coalitions 显示文摘 | Boyd J H Prescott E C | 1986 | Journal of Economic Theory1986，38，： | 1 |
| 12 | Transplacental priming of the human immune system to environmental allergens: Universal skewing of initial T cell responses toward the Th2 eytokineprofile显示文摘 | Prescott SL Maeaubas C Holt BJ | 1998 | J Immunol1998，160，10： | 1 |
| 13 | The equity premium: A puzzle 显示文摘 | Mehra R Prescott E C | 1985 | Journal of Monetary Economics1985，15，2： | 1 |
| 14 | Influence of forest floor type on rates of litter decomposition in microcosms显示文摘 | PRESCOTT C E | 1996 | Soil Biol Biochem1996，28，1011： | 1 |
| 15 | Microbial communities in forest floors under four tree species in coastal British Columbia 显示文摘 | GRAYSTON S J PRESCOTT C E | 2005 | Soil Biology and Biochemistry2005，37，6： | 1 |
| 16 | Spectral sensitivity of the domestic fowl显示文摘 | Prescott N B Wathes C M | 1999 | British Poultry Science1999，40，： | 1 |
| 17 | Influence of forest floor type on rates of litter decomposition in microcosms显示文摘 | PRESCOTT C E | 1996 | Soil Biol Biochem1996，28，： | 1 |
| 18 | Prognostic value of nutritional status in chronic obstructive pulmonary disease显示文摘 | Landbo C Prescott E Lange P | 1999 | Am J Respir Crit Care Med1999，160，： | 1 |
| 19 | Postwar US business cycles: an empirical investigation 显示文摘 | Hodrick R J Prescott E C | 1997 | Journal of Money credit and Banking1997，1997，： | 1 |
| 20 | Xenon purity analysis for exo-200 via mass spectrometry 显示文摘 | Dobi A Hall C Slutsky S Yen Y R Aharmin B Auger M Barbeau P S Benitez-Medina C Breidenbach M Cleveland B Conley R Cook J Cook S Counts I Craddock W Daniels T Davis C G Davis J Devoe R Dixit M Dolinski M J Donato K Fairbank Jr W Farine J Fierlinger P Franco D Giroux G Gornea R Graham K Gratta G Green C Hagemann C Hall K Hallman D Hargrove C Herrin S Hughes M Hodgson J Juget F Karelin A Kaufman L J Kuchenkov A Kumar K Leonard D S Lutter G Mackay D Maclellan R Marino M Mong B Montero Diez M Morgan P MUller A R Neilson R Odian A Oullivan K Piepke A Pocar A Prescott C Y Pushkin K Rivas A Rollin E Rowson P C Sabourov A Sinclair D Skarpaas K Stekhanov V Strickland V Swift M Twelker K Vuilleumier J L Vuilleumier J M Weber M Wichoski U Wodin J Wright J D Yang L | 2012 | Nuclear Instruments and Methods in Physics Research Section A: Accelerators Spectrometers Detectors and Associated Equipment2012，675，： | 1 |
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