Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2021; 27(38): 6489-6500
Published online Oct 14, 2021. doi: 10.3748/wjg.v27.i38.6489
Serum soluble suppression of tumorigenicity 2 as a novel inflammatory marker predicts the severity of acute pancreatitis
Yan Zhang, Bo Cheng, Zhong-Wei Wu, Zong-Chao Cui, Yao-Dong Song, San-Yang Chen, Yan-Na Liu, Chang-Ju Zhu
Yan Zhang, Bo Cheng, Zhong-Wei Wu, Zong-Chao Cui, Yao-Dong Song, San-Yang Chen, Yan-Na Liu, Chang-Ju Zhu, Department of Emergency, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Author contributions: Zhu CJ conceived and designed the study; Zhang Y, Cheng B, Liu YN and Wang QF performed the research; Wu ZW contributed the data acquisition; Zhang Y and Cui ZC conducted data analysis/interpretation; Song YD contributed statistical analysis; Zhang Y and Chen SY wrote the manuscript; All authors have read and approved the final manuscript.
Supported by Henan Province Education Department for Henan Province University Key Scientific Research Project, No. 20A320018 and No. 20A320064.
Institutional review board statement: The study was reviewed and approved by the First Affiliated Hospital of Zhengzhou University Institutional Review Board [(Approval No. 2018-KY-140)].
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors have no potential conflict of interest to disclose.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at zhuchangju98@163.com. 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: Chang-Ju Zhu, PhD, Chief Doctor, Chief Physician, Director, Doctor, Professor, Department of Emergency, the First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou 450052, Henan Province, China. zhuchangju98@163.com
Received: April 4, 2021
Peer-review started: April 4, 2021
First decision: May 27, 2021
Revised: June 10, 2021
Accepted: August 27, 2021
Article in press: August 27, 2021
Published online: October 14, 2021
Abstract
BACKGROUND

Acute pancreatitis (AP) is an inflammatory disease in which the regulatory pathway is complex and not well understood. Soluble suppression of tumorigenicity 2 (sST2) protein receptor functions as a decoy receptor for interleukin (IL)-33 to prevent IL-33/suppression of tumorigenicity 2L (ST2L)-pathway-mediated T helper (Th)2 immune responses.

AIM

To investigate the role of sST2 in AP.

METHODS

We assessed the association between sST2 and severity of AP in 123 patients enrolled in this study. The serum levels of sST2, C-reactive protein (CRP) and Th1- and Th2-related cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-5 and IL-13, were measured by highly sensitive ELISA, and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria.

RESULTS

Serum sST2 levels were significantly increased in AP patients, and further, these levels were significantly elevated in severe AP (SAP) patients compared to moderately severe AP (MSAP) and mild AP (MAP) patients. Logistic regression showed sST2 was a predictor of SAP [odds ratio (OR): 1.003 (1.001–1.006), P = 0.000]. sST2 cutoff point was 1190 pg/mL, and sST2 above this cutoff was associated with SAP. sST2 was also a predictor of any organ failure and mortality during AP [OR: 1.006 (1.003–1.009), P = 0.000, OR: 1.002 (1.001–1.004), P = 0.012, respectively]. Additionally, the Th1-related cytokines IFN-γ and TNF-α in the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups.

CONCLUSION

sST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis.

Keywords: Acute pancreatitis, Soluble suppression of tumorigenicity 2, T-helper 1 cells, T-helper 2 cells, Interleukin-33, Biomarker

Core Tip: Acute pancreatitis (AP) is an inflammatory disease in which the regulatory pathway is complex and not well understood. The interleukin (IL)-33/ suppression of tumorigenicity 2L (ST2L) functional pathway is involved in the pathological process of AP. Soluble suppression of tumorigenicity 2 protein (sST2) is a soluble receptor, which is released in the circulation acts as a decoy receptor by binding IL-33. However, sST2 as one of the most promising disease biomarker, has not been studied in the development of AP. In this study we studied the role of sST2 as an inflammatory marker for predicting the severity of acute pancreatitis.