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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 | Proliferative activity is asignificant prognostic factor in male breast carcinoma 显示文摘 | Pich A Margaria E Chinsa L | 1994 | Am J Pathol1994，145，： | 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 | 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 |
| 6 | 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 |
| 7 | Marital and sexual aspects of old age显示文摘 | Trudel G Turgeon L Piche L | 2000 | Sexual & elationship Therapy2000，15，4： | 1 |
| 8 | Ultrasonic probe for on-line process monitoring显示文摘 | Piche L Gendron R Hamel A | 1999 | Plastics Engineering1999，55，10： | 1 |
| 9 | 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 |
| 10 | PCR mapping ot integrons reveals several novel combinations of resistance genes显示文摘 | Levesque C Piche L Larose C | | 0，，： | 1 |
| 11 | 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 |
| 12 | Use of clinoptilolite for the immobilization of heavy metal ions and preparation of autoclaved building composites显示文摘 | W. Mozgawa M. Król W. Pichór | 2009 | Journal of Hazardous Materials2009，，2： | 1 |
| 13 | Proliferative activity is a significant prognostic factor in male breast carcinoma显示文摘 | Pich A Margaria E Chiusa L | 1994 | Am J Pathol1994，145，3： | 1 |
| 14 | 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 |
| 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 | The Mitochondrial Production of Reactive Oxygen Species in Relation to Aging and Pathology显示文摘 | Genova M L Pich M M Bernacchia A | 2004 | Ann NY Acad Sci2004，1011，： | 1 |
| 17 | The mitochondrial production of reactive oxygen species in relation to aging and pathology显示文摘 | GENOVA M L PICH M M BERNACCHIA A | 2004 | Ann N Y Acad Sci2004，1011，： | 1 |
| 18 | A test of Ras- mussen' s risk management framework in the food safety domain: BSE in the UK 显示文摘 | Cassano - Piche A L Vieente K J Jamieson G A | 2009 | Theoretical Issues in Ergonomics Science2009，10，4： | 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 | Proliferative activity is the most significant predictor of recurrence in noninvasive papillary urothelial neoplasms of low malignant potential and grade 1 papillary carcinomas of the bladder显示文摘 | Pich A Chiusa L Formiconi A | 2002 | Cancer2002，95，4： | 1 |
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