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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2021; 27(2): 162-175
Published online Jan 14, 2021. doi: 10.3748/wjg.v27.i2.162
Detection of fucosylated haptoglobin using the 10-7G antibody as a biomarker for evaluating endoscopic remission in ulcerative colitis
Kei Motooka, Koichi Morishita, Nami Ito, Shinichiro Shinzaki, Taku Tashiro, Satoshi Nojima, Kayoko Shimizu, Mutsuhiro Date, Natsumi Sakata, Momoko Yamada, Shinji Takamatsu, Yoshihiro Kamada, Hideki Iijima, Tsunekazu Mizushima, Eiichi Morii, Tetsuo Takehara, Eiji Miyoshi
Kei Motooka, Koichi Morishita, Nami Ito, Natsumi Sakata, Momoko Yamada, Shinji Takamatsu, Yoshihiro Kamada, Eiji Miyoshi, Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
Shinichiro Shinzaki, Taku Tashiro, Hideki Iijima, Tetsuo Takehara, Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
Satoshi Nojima, Eiichi Morii, Department of Pathology, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
Kayoko Shimizu, Mutsuhiro Date, FUJIFILM Wako Pure Chemical Corporation, Amagasaki 661-0963, Hyogo, Japan
Tsunekazu Mizushima, Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita 565-0871, Osaka, Japan
Author contributions: Miyoshi E contributed to the conception and design of the study; Motooka K, Morishita K, Ito N, Sakata N, Yamada M, Takamatsu S and Kamada Y contributed to the acquisition and analysis of data; Shimizu K and Date M produced ELISA kits and interpretation of data; Shinzaki S, Tashiro T, Nojima S, Iijima H, Mizushima T, Morii E and Takehara T provided clinical samples and data; Motooka K, Morishita K and Miyoshi E contributed to the drafting the article or revising it critically for important intellectual content; all authors approved the final version of the article.
Supported by Ministry of Education, Culture, Sports, Science and Technology of Japan, No. 19H03562; and FUJIFILM Wako Pure Chemical Corporation, No. J770701626.
Institutional review board statement: This study was approved by the ethics committee of Osaka University Hospital and conducted in accordance with approved guidelines (Approval No. 14107-10).
Informed consent statement: Written informed consent was obtained from all subjects in this study at the time of enrollment or blood sampling.
Conflict-of-interest statement: Shimizu K and Date M are employees of FUJIFILM Wako Pure Chemical Corporation and the authors received approximately $5000 per year from a collaboration grant with FUJIFILM Wako Pure Chemical Corporation. The authors declare no other conflicts of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/ Corresponding author: Eiji Miyoshi, MD, PhD, Professor, Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita 565-0871, Osaka, Japan.
emiyoshi@sahs.med.osaka-u.ac.jp
Received: September 23, 2020
Peer-review started: September 23, 2020
First decision: November 8, 2020
Revised: November 11, 2020
Accepted: December 23, 2020
Article in press: December 23, 2020
Published online: January 14, 2021
Processing time: 108 Days and 13.2 Hours
BACKGROUND
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammation of the digestive tract. Although fecal and serum biomarkers have been extremely important and supportive for monitoring of IBD, their low sensitivity and high variability characteristics limit clinical efficacy. Thus, the establishment of better biomarkers is expected. Fucosylation is one of the most important glycosylation modifications of proteins. Fucosylated haptoglobin (Fuc-Hpt) is used as a biomarker for several cancers and inflammation-related diseases. We recently established a novel glycan monoclonal antibody (mAb), designated 10-7G, which recognizes Fuc-Hpt. We developed an enzyme-linked immunosorbent assay (ELISA) to measure serum levels of Fuc-Hpt (10-7G values).
AIM
To investigate the usefulness of the serum 10-7G values as a potential biomarker for monitoring disease activity in IBD.
METHODS
This was a case control study. Intestinal tissues of IBD patients (n = 10) were examined immunohistochemically using the 10-7G mAb. We determined 10-7G values using serum from patients with ulcerative colitis (UC, n = 110), Crohn’s disease (n = 45), acute enteritis (AE, n = 11), and healthy volunteers (HVs) who exhibited normal (n = 20) or high (n = 79) C-reactive protein (CRP) levels at medical check-up. We investigated the correlation between the 10-7G value and various clinical parameters of IBD patients by correlation analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the usefulness of the 10-7G values as a biomarker for clinical and endoscopic remission of UC compared to conventional serum biomarkers.
RESULTS
In the immunohistochemical analysis, positive 10-7G mAb staining was observed in lymphocytes infiltrating into inflammatory sites of the mucosal layer and lymphoid follicles. The 10-7G values were significantly higher in patients with IBD (P < 0.001) and AE (P < 0.05) compared with HVs. In addition, 10-7G values were correlated with clinical examination parameters related to inflammation in patients with UC, particularly the CRP level (rs = 0.525, P = 0.003) and clinical activity index score (rs = 0.435, P = 0.038). However, there was no correlation between 10-7G values and CRP in HVs with high CRP levels, suggesting that the 10-7G values is not the same as a general inflammation biomarker. ROC curve analysis showed that area under the curve (AUC) value of 10-7G values for the diagnosis of endoscopic remission was higher than other biomarkers (AUC value = 0.699).
CONCLUSION
The serum 10-7G value is a novel biomarker for evaluating intestinal inflammation and endoscopic mucosal healing in UC.
Core Tip: Fucosylation is one of the most important glycosylation involved in cancer and inflammation. Recently, we have succeeded to establish a novel glycan antibody 10-7G mAb which directly recognizes fucosylated haptoglobin (Fuc-Hpt), and developed its enzyme-linked immunosorbent assay (ELISA) system. In this study, we demonstrated the serum 10-7G values (Fuc-Hpt levels determined with 10-7G mAb ELISA) were significantly higher in patients with inflammatory bowel disease. We also found that Fuc-Hpt was produced by lymphocytes infiltrating into inflammatory sites of intestine. Moreover, statistical analyses showed that the 10-7G value could evaluate intestinal inflammation and endoscopic mucosal healing in ulcerative colitis.
