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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2016; 22(41): 9104-9116
Published online Nov 7, 2016. doi: 10.3748/wjg.v22.i41.9104
Published online Nov 7, 2016. doi: 10.3748/wjg.v22.i41.9104
Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy
Angela C Baird, Ian C Lawrance, Faculty of Medicine and Dentistry, School of Medicine and Pharmacology, University of Western Australia, Perth, WA 6009, Australia
Dominic Mallon, Department of Immunology, Fremantle Hospital, Perth, WA 6160, Australia
Graham Radford-Smith, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, 4006, Australia
Julien Boyer, Thierry Piche, Meri K Tulic, University of Nice Sophia-Antipolis, EA6302, 06202 Nice, France
Julien Boyer, Thierry Piche, Department of Gastroenterology and Nutrition, l’Archet Hospital 2, 06202 Nice, France
Susan L Prescott, School of Paediatrics and Child Health, University of Western Australia, Subiaco, WA 6008, Australia
Susan L Prescott, Meri K Tulic, International Inflammation network (in-FLAME) of the World Universities Network, University of Western Australia, Subiaco, WA 6008, Australia
Ian C Lawrance, Centre for Inflammatory Bowel Diseases, St John of God Subiaco Hospital, Perth, WA 6009, Australia
Meri K Tulic, Mediterranean Center for Molecular Medicine (C3M)-INSERM U1065, Team 12, 06204 Nice, France
Author contributions: Baird AC and Tulic MK were involved in data acquisition, analysis, interpretation of the data and writing of the manuscript; Baird AC, Mallon D, Radford-Smith G, Lawrance IC and Tulic MK were involved in study design; Prescott SL provided protocols and provision of laboratory space for some experiments; Boyer J, Piche T and Lawrance IC gave invaluable intellectual input into the study and clinical direction; Lawrance IC and Tulic MK proposed the original hypothesis of this study and approved the final version of this manuscript.
Institutional review board statement: The study was reviewed and approved by the Southern Metropolitan Health Service Human Ethics Committee and Institutional Review Board.
Informed consent statement: All biological samples from the patients were taken after informed consent.
Conflict-of-interest statement: To the best of our knowledge, there is no conflict of interest to declare.
Data sharing statement: Two senior co-authors (Lawrance IC and Tulic MK) have access to all data and dataset available from the corresponding author at meri.tulic@unice.fr.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Meri K Tulic, PhD, INSERM, CR1, Professor, Mediterranean Center for Molecular Medicine (C3M)-INSERM U1065, Team 12, Batiment Archimed, 151 route Saint-Antoine de Ginestiere, 06204 Nice, France. meri.tulic@unice.fr
Telephone: +33-4-89064326 Fax: +33-4-89064221
Received: July 8, 2016
Peer-review started: July 12, 2016
First decision: July 29, 2016
Revised: August 25, 2016
Accepted: September 28, 2016
Article in press: September 28, 2016
Published online: November 7, 2016
Processing time: 120 Days and 21.9 Hours
Peer-review started: July 12, 2016
First decision: July 29, 2016
Revised: August 25, 2016
Accepted: September 28, 2016
Article in press: September 28, 2016
Published online: November 7, 2016
Processing time: 120 Days and 21.9 Hours
Core Tip
Core tip: Anti-tumor necrosis factor (TNF) therapy is effective in approximately 60% of ulcerative colitis (UC) patients. Currently we do not know which patients are likely to benefit from this costly treatment. Here we show that differences in innate immune function [measured by patients response to toll-like-receptor (TLR), TLR agonists] exist between UC responders and non-responders. Differences exist in (1) content of immune and regulatory cells in their blood; (2) capacity of their cells to produce cytokines; and (3) in their signalling following TLR activation. Serological measure of TLR function may prove to be a useful tool in clinic to predict patient’s response to anti-TNF treatment.