Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2021; 27(1): 92-106
Published online Jan 7, 2021. doi: 10.3748/wjg.v27.i1.92
Valuable clinical indicators for identifying infantile-onset inflammatory bowel disease patients with monogenic diseases
Wen Su, Yi Yu, Xu Xu, Xin-Qiong Wang, Jie-Bin Huang, Chun-Di Xu, Yuan Xiao
Wen Su, Yi Yu, Xu Xu, Xin-Qiong Wang, Jie-Bin Huang, Chun-Di Xu, Yuan Xiao, Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China
Author contributions: Su W and Yu Y contributed equally to this work; Su W and Yu Y were in charge of the data analysis and writing; Xu X and Wang XQ contributed to data collection; Huang JB contributed to literature search and figure preparation; Xu CD and Xiao Y contributed to study design and data interpretation, and they contributed equally to this work; all authors have read and approved the final manuscript.
Supported by Scientific Research Fund of Shanghai Municipal Health Commission, No. 201640368; National Natural Science Foundation of China, No. 81741103; and The Shanghai Plan for Women and Children's Health Service Capacity Construction (Enhancing the Service Capacity of Shanghai Women and Children Health Care Institutions).
Institutional review board statement: This study was approved by the ethics committee of Ruijin Hospital, Shanghai Jiaotong University School of Medicine.
Informed consent statement: All guardians of the enrolled pediatric patients who experienced the gene test signed an informed consent form.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
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: Yuan Xiao, MD, PhD, Associate Chief Physician, Doctor, Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, No. 197 Ruijin 2 Road, Shanghai 200025, China. yxiao.penicilinum@gmail.com
Received: October 16, 2020
Peer-review started: October 16, 2020
First decision: November 23, 2020
Revised: December 2, 2020
Accepted: December 11, 2020
Article in press: December 11, 2020
Published online: January 7, 2021
ARTICLE HIGHLIGHTS
Research background

Infantile-onset inflammatory bowel disease (IO-IBD) causes severe clinical manifestations and responds poorly to traditional inflammatory bowel disease (IBD) treatments. At present, there are no simple and reliable laboratory indicators for early screening IO-IBD patients, especially those in whom the disease is caused by monogenic diseases.

Research motivation

Because of an insufficient understanding of IO-IBD, especially that caused by monogenic diseases, most patients could not be diagnosed as early as possible. It is hard to persuade the parents to accept endoscopic examination or genetic diagnosis at initial visits, especially those in areas with limited medical resources.

Research objectives

We intended to search for early diagnostic indicators for IO-IBD children with or without gene mutations, in order to shorten the diagnosis time, reduce medical costs, simplify the analysis of next generation-sequencing, and administer targeted intervention as early as possible.

Research methods

A retrospective analysis was performed in 73 patients with IO-IBD admitted to our hospital in the past 5 years. Based on the next-generation sequencing results, they were divided into either a monogenic IBD group (M-IBD) or non-monogenic IBD group (NM-IBD). Forty age-matched patients with allergic proctocolitis (AP) were included as a control group. The clinical manifestations and the inflammatory factors in peripheral blood were evaluated. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to find the screening factors and cut-off values of IO-IBD as well as monogenic IO-IBD.

Research results

Among the 44 M-IBD patients, 35 carried IL-10RA mutations, and the most common mutations were c.301C>T (p.R101W, 30/70) and c.537G>A (p.T179T, 17/70). Patients with higher serum tumor necrosis factor (TNF)-α value were more likely have IBD [odds ratio (OR) = 1.25, 95% confidence interval (CI): 1.05-1.50, P = 0.013), while higher serum albumin level was associated with lower risk of IBD (OR = 0.86, 95%CI: 0.74-1.00, P = 0.048). The cut-off values of TNF-α and albumin were 17.40 pg/mL (sensitivity: 0.78; specificity: 0.88) and 36.50 g/L (sensitivity: 0.80; specificity: 0.90), respectively. The increased ferritin level was indicative of a genetic mutation in IO-IBD patients. Its cut-off value was 28.20 ng/mL (sensitivity: 0.93; specificity: 0.92). When interleukin (IL)-10 level was higher than 33.05 pg/mL (sensitivity: 1.00; specificity: 0.84), or the onset age was earlier than 0.21 mo (sensitivity: 0.82; specificity: 0.94), the presence of disease-causing mutations in IL-10RA in IO-IBD patients was strongly suggested.

Research conclusions

Serum TNF-α and albumin level could differentiate IO-IBD patients from allergic proctocolitis patients, and serum ferritin and IL-10 level are useful indicators for early diagnosing monogenic IO-IBD.

Research perspectives

Using serum TNF-α and albumin level may contribute to distinguishing IO-IBD which needs further investigations, such as gastrointestinal endoscopy. High levels of serum ferritin and IL-10 can infer a monogenic disease in IO-IBD patients, especially the mutations in the IL-10RA gene. The diagnostic value of the indicators identified in this study should be evaluated by prospective studies.