Published online Jan 14, 2021. doi: 10.3748/wjg.v27.i2.162
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
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).
To investigate the usefulness of the serum 10-7G values as a potential biomarker for monitoring disease activity in IBD.
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.
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).
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.