Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2024; 30(13): 1899-1910
Published online Apr 7, 2024. doi: 10.3748/wjg.v30.i13.1899
Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease
Ante Tonkic, Marko Kumric, Ivna Akrapovic Olic, Doris Rusic, Piero Marin Zivkovic, Daniela Supe Domic, Zeljko Sundov, Ivan Males, Josko Bozic
Ante Tonkic, Biology of Neoplasms, University of Split School of Medicine, Split 21000, Croatia
Marko Kumric, Josko Bozic, Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
Ivna Akrapovic Olic, Piero Marin Zivkovic, Zeljko Sundov, Department of Gastroenterology, University Hospital of Split, Split 21000, Croatia
Doris Rusic, Department of Pharmacy, University of Split School of Medicine, Split 21000, Croatia
Daniela Supe Domic, Department of Medical Laboratory Diagnostics, University Hospital of Split, Split 21000, Croatia
Daniela Supe Domic, Department of Health Studies, University of Split, Split 21000, Croatia
Zeljko Sundov, Department of Internal Medicine, University of Split School of Medicine, Split 21000, Croatia
Ivan Males, Department of Surgery, University Hospital of Split, Split 21000, Croatia
Author contributions: Tonkic A participated in conceptualization, methodology, investigation, formal analysis, and original draft preparation; Kumric M participated in visualization, investigation, formal analysis, and original draft preparation; Akrapovic Olic I participated in visualization, investigation, formal analysis, and original draft preparation; Rusic D participated in visualization, investigation, formal analysis, and reviewing and editing of the manuscript; Zivkovic PM participated in visualization, investigation, formal analysis, and original draft preparation; Supe Domic D participated in visualization, investigation, formal analysis, and original draft preparation; Sundov Z participated in visualization, investigation, formal analysis and reviewing, and editing of the manuscript; Males I participated in visualization, investigation, formal analysis, and original draft preparation; Bozic J participated in conceptualization, funding acquisition, resources, project administration, and reviewing and editing of the manuscript; and all authors contributed to the final draft of the manuscript, read and agreed to the published version of the manuscript.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the University Hospital of Split (Approval No. 2181-147/01/06/M.S.-21-02).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrolment.
Conflict-of-interest statement: There are no conflicts of interest to report.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Josko Bozic, MD, PhD, Associate Professor, Department of Pathophysiology, University of Split School of Medicine, 2 Soltanska, Split 21000, Croatia. josko.bozic@mefst.hr
Received: January 4, 2024
Peer-review started: January 4, 2024
First decision: January 17, 2024
Revised: January 29, 2024
Accepted: March 13, 2024
Article in press: March 13, 2024
Published online: April 7, 2024
Processing time: 89 Days and 15.2 Hours
ARTICLE HIGHLIGHTS
Research background

Although commonly perceived as disease of the gastrointestinal system, inflammatory bowel disease can affect other organ systems, including cardiovascular, potentially leading to increased morbidity and mortality. Growth-differentiation factor-15 (GDF-15) is often over-expressed in stress conditions, including inflammation, malignancies, heart failure, and myocardial ischemia. In fact, elevated serum concentrations of GDF-15 have been linked to poor outcomes in conditions with diverse pathogenesis, such as colorectal cancer and heart failure.

Research motivation

As serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in diverse ailments, we aimed to explore whether such association is present in the setting of inflammatory bowel disease (IBD) and its consequences. Establishing the role of GDF-15 in IBD might be relevant since poor long-term outcomes in IBD population are currently not fully elucidated.

Research objectives

To establish whether serum levels of GDF-15 in patients with IBD are different then in the healthy controls. Furthermore, we aimed to establish whether GDF-15 level correlate with disease severity, thus providing a rationale for the future assessment of its prognostic role in IBD. Finally, we investigated if association between indices of anemia and GDF-15 serum levels exists in this population.

Research methods

In this cross-sectional study, patients with IBD and healthy age- and sex-matched participants underwent an extensive diagnostic workup. IBD group also underwent colonoscopy with subsequent histopathological analysis, and the disease activity was assessed using well-established clinical and endoscopic scoring systems. GDF-15 serum concentrations were determined using electrochemiluminescence immunoassay.

Research results

The principal findings of the present study reveal significantly elevated levels of GDF-15 in patients with IBD compared to the control group, and these levels increase with greater disease severity. Since no similar data have been previously published, the reasons behind this observation remain elusive. Nevertheless, considering the independent association between GDF-15 and indices of anemia, it is plausible that pathophysiological changes in anemia and iron metabolism might, to some extent, explain the observed difference.

Research conclusions

This study marks the first demonstration of significantly elevated serum concentrations of GDF-15 in patients with IBD. While mechanistic studies and prospective trials are essential for firm conclusions, these preliminary findings suggest that exploring the role of GDF-15 as a biomarker in IBD could be worthwhile.

Research perspectives

Future research should delve into the prognostic role of GDF-15, with a specific focus on its relationship with disease severity. Furthermore, investigating the mechanisms underlying these preliminary results will contribute to a deeper understanding of the role of GDF-15 in IBD.