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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2015; 21(6): 1907-1914
Published online Feb 14, 2015. doi: 10.3748/wjg.v21.i6.1907
Published online Feb 14, 2015. doi: 10.3748/wjg.v21.i6.1907
Significance of low level infliximab in the absence of anti-infliximab antibodies
Bella Ungar, Adi Anafy, Miri Yavzori, Orit Picard, Ella Fudim, Uri Kopylov, Rami Eliakim, Shomron Ben-Horin, Department of Gastroenterology, Sheba Medical Center Tel Hashomer and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel
Henit Yanai, Yulia Ron, Iris Dotan, IBD Center, Department of Gastroenterology, Tel-Aviv Sourasky Medical Center and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel
Ronen Loebstein, Institute of Clinical Pharmacology, Sheba Medical Center Tel Hashomer and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel
Yehuda Chowers, Rambam Health Care Campus and Bruce Rappaport School of Medicine, Technion Institute of Technology, Haifa 31999, Israel
Author contributions: Ungar B, Anafi A and Yanai H analyzed the data; Ungar B drafted the manuscript; Yavzori M, Fudim E and Picard O performed the laboratory research; Kopylov U, Ron Y, Loebstein R, Dotan I and Eliakim R assisted in data acquisition and drafted the manuscript; Ben-Horin S conceived the study, designed the research and drafted the manuscript; all authors finally approved the manuscript.
Supported by (in part) “Talpiot” Medical Leadership program of the Sheba Medical Center (to SBH) and the Helmsley Charitable Trust (To SBH, RE, ID and YC).
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: Bella Ungar, MD, Department of Gastroenterology, Sheba Medical Center Tel Hashomer and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel. bellageyshis@gmail.com
Telephone: +972-3-5302694 Fax: +972-3-5303160
Received: August 8, 2014
Peer-review started: August 9, 2014
First decision: August 27, 2014
Revised: September 8, 2014
Accepted: October 14, 2014
Article in press: October 15, 2014
Published online: February 14, 2015
Processing time: 187 Days and 1.1 Hours
Peer-review started: August 9, 2014
First decision: August 27, 2014
Revised: September 8, 2014
Accepted: October 14, 2014
Article in press: October 15, 2014
Published online: February 14, 2015
Processing time: 187 Days and 1.1 Hours
Core Tip
Core tip: Among patients who lose response to infliximab (IFX) 10%-60% have low IFX levels in the absence of antibodies to infliximab (ATI) - double negative (DN) status. We explored the prevalence and the mechanisms responsible for DN status. The prevalence of DN sera varied with the assay and dilution used. Patients with DN status had shorter survival free of ATI compared with matched controls (P < 0.001). We believe that DN status may result from false negative detection of IFX or ATI by a conventional ELISA assay, suggesting a transitional state of low-level immunogenicity, rather than non-immunological drug clearance.