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
Abstract
BACKGROUND

Population of patients with inflammatory bowel disease (IBD) is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality. Growth-differentiation factor-15 (GDF-15) is often over-expressed under stress conditions, such as inflammation, malignancies, heart failure, myocardial ischemia, and many others.

AIM

To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases. An additional aim was to determine possible associations between GDF-15 and multiple clinical, anthropometric and laboratory parameters in patients with IBD.

METHODS

This cross-sectional study included 90 adult patients diagnosed with IBD, encompassing both Crohn’s disease (CD) and ulcerative colitis (UC), and 67 healthy age- and sex-matched controls. All patients underwent an extensive workup, including colonoscopy with subsequent histopathological analysis. Disease activity was assessed by two independent gastroenterology consultants specialized in IBD, employing well-established clinical and endoscopic scoring systems. GDF-15 serum concentrations were determined following an overnight fasting, using electrochemiluminescence immunoassay.

RESULTS

In patients with IBD, serum GDF-15 concentrations were significantly higher in comparison to the healthy controls [800 (512-1154) pg/mL vs 412 (407-424) pg/mL, P < 0.001], whereas no difference in GDF-15 was found between patients with CD and UC [807 (554-1451) pg/mL vs 790 (509-956) pg/mL, P = 0.324]. Moreover, multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age, sex, and C-reactive protein levels (P = 0.016 and P = 0.049, respectively). Finally, an association between GDF-15 and indices of anemia was established. Specifically, negative correlations were found between GDF-15 and serum iron levels (r = -0.248, P = 0.021), as well as GDF-15 and hemoglobin (r = -0.351, P = 0.021). Accordingly, in comparison to IBD patients with normal hemoglobin levels, GDF-15 serum levels were higher in patients with anemia (1256 (502-2100) pg/mL vs 444 (412-795) pg/mL, P < 0.001).

CONCLUSION

For the first time, we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls, and the results imply that GDF-15 might be involved in IBD pathophysiology. Yet, it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients.

Keywords: Inflammatory bowel disease; Crohn’s disease; Ulcerative colitis; Growth-differentiation factor-15; Anemia; Extraintestinal manifestations

Core Tip: Serum concentrations of growth-differentiation factor-15 (GDF-15) exhibit a significant elevation in inflammatory bowel disease (IBD) patients compared to healthy controls, irrespective of Crohn’s disease or ulcerative colitis diagnosis. GDF-15 levels independently predict disease severity and demonstrate an association with anemia indices, indicating its potential as a biomarker for IBD pathophysiology. Further exploration is nonetheless warranted to determine the prognostic value of GDF-15 in predicting outcomes for patients with IBD.