Gasdermin D: A New Inflammatory Biomarker in Assessing Clinical Disease Activity in Crohn’s Disease
Main Article Content
Abstract
Background/Aims: Crohn’s disease (CD) is an inflammatory, progressive disorder requiring monitoring of treatment response and disease course. Gasdermin D (GSDMD), a protein belonging to the gasdermin protein family, plays a role in inflammatory cell death, and activation of GSDMD has been shown to be a component of the pathogenesis of inflammatory bowel disease. Considering the role that GSDMD plays in inflammation, it was hypothesized that disease activity in CD may be correlated with serum GSDMD levels. The aim of this study was to assess the strength of GSDMD in predicting clinical disease activity in patients with CD in a prompt and easy manner.
Materials and Methods: This cross-sectional study was conducted over a span of 22 months from September 2022 to June 2024. A total of 61 patients with CD were included in the study. Demographic data, disease- and treatment-related data, and laboratory workups of the patients were recorded and analyzed.
Results: Gasdermin D levels were statistically significant in their correlation with the Harvey–Bradshaw Index (HBI) scores of the study population (P = .019). A threshold value of 5 ng/mL for GSDMD had a sensitivity of 84.6% and a specificity of 91.7% in differentiating patients with remission or mild disease from those with moderate or severe disease, according to HBI.
Conclusion: This pioneering study revealed that serum GSDMD can be used as a biomarker to assess clinical disease activity in patients with CD. Future studies incorporating colonoscopic evaluation into the equation will provide more insight into the use of this protein as a surrogate marker of disease progression in CD.
Cite this article as: Buldukoglu OC, Ocal S, Atar GE, et al. Gasdermin D: A new inflammatory biomarker in assessing clinical disease activity in Crohn’s disease. Turk J Gastroenterol. Published online May 20, 2025. doi 10.5152/tjg.2025.24726.
Article Details
References
1. Törüner M, Ünal NG. Epigenetics of inflammatory bowel diseases. Turk J Gastroenterol. 2023;34(5):437-448. [CrossRef]
2. Meima-van Praag EM, Buskens CJ, Hompes R, Bemelman WA. Surgical management of Crohn’s disease: a state of the art review. Int J Colorectal Dis. 2021;36(6):1133-1145. [CrossRef]
3. Wetwittayakhlang P, Verdon C, Starr M, et al. Mucosal healing and clinical efficacy of adalimumab in small intestinal Crohn’s disease (SIMCHA study): final results from a prospective, open-label, single-arm study. Turk J Gastroenterol. 2023;34(6):603-610. [CrossRef]
4. Ananthakrishnan AN, Adler J, Chachu KA, et al. AGA clinical practice guideline on the role of biomarkers for the management of Crohn’s disease. Gastroenterology. 2023;165(6):1367-1399. [CrossRef]
5. Dai Z, Liu WC, Chen XY, Wang X, Li JL, Zhang X. Gasdermin D-mediated pyroptosis: mechanisms, diseases, and inhibitors. Front Immunol. 2023;14:1178662. [CrossRef]
6. Best WR. Predicting the Crohn’s disease activity index from the Harvey-Bradshaw Index. Inflamm Bowel Dis. 2006;12(4):304-310. [CrossRef]
7. Cankurtaran RE, Güneş YC, Dirican E, Algın O, Cankurtaran D, Tayfur Yürekli Ö. Sarcopenia and myosteatosis assessed by magnetic resonance enterography may predict negative outcomes in patients with Crohn’s disease. Turk J Gastroenterol. 2023;34(8):839-849. [CrossRef]
8. Eugenicos MP, Ferreira NB. Psychological factors associated with inflammatory bowel disease. Br Med Bull. 2021;138(1):16-28. [CrossRef]
9. Shaffer VO, Wexner SD. Surgical management of Crohn’s disease. Langenbecks Arch Surg. 2013;398(1):13-27. [CrossRef]
10. Rogler G, Singh A, Kavanaugh A, Rubin DT. Extraintestinal manifestations of inflammatory bowel disease: current concepts, treatment, and implications for disease management. Gastroenterology. 2021;161(4):1118-1132. [CrossRef]
11. Lontai L, Kürti Z, Gonczi L, et al. Objective disease monitoring strategies from a Tertiary Inflammatory Bowel Disease Center in Hungary. Turk J Gastroenterol. 2023;34(5):508-515. [CrossRef]
12. Rymarczyk D, Schultz W, Borowa A, et al. Deep learning models capture histological disease activity in Crohn’s disease and ulcerative colitis with high fidelity. J Crohns Colitis. 2024;18(4):604-614. [CrossRef]
13. Liu X, Xia S, Zhang Z, Wu H, Lieberman J. Channelling inflammation: gasdermins in physiology and disease. Nat Rev Drug Discov. 2021;20(5):384-405. [CrossRef]
14. Pan Y, Cai W, Huang J, et al. Pyroptosis in development, inflammation and disease. Front Immunol. 2022;13:991044. [CrossRef]
15. Zhang S, Liang Y, Yao J, Li DF, Wang LS. Role of pyroptosis in inflammatory bowel disease (IBD): from gasdermins to DAMPs. Front Pharmacol. 2022;13:833588. [CrossRef]
16. Gao X, Wang C, Shen XT, et al. Pyroptosis burden is associated with anti-TNF treatment outcome in inflammatory bowel disease: new insights from bioinformatics analysis. Sci Rep. 2023;13(1):15821. [CrossRef]
17. Xiao J, Sun K, Wang C, Abu-Amer Y, Mbalaviele G. Compound loss of GSDMD and GSDME function is necessary to achieve maximal therapeutic effect in colitis. J Transl Autoimmun. 2022;5:100162. [CrossRef]
18. Bulek K, Zhao J, Liao Y, et al. Epithelial-derived gasdermin D mediates nonlytic IL-1β release during experimental colitis. J Clin Invest. 2020;130(8):4218-4234. [CrossRef]
19. Gao H, Cao M, Yao Y, et al. Dysregulated microbiota-driven gasdermin D activation promotes colitis development by mediating IL-18 release. Front Immunol. 2021;12:750841. [CrossRef]
20. Ma Y, Chen Y, Lin C, Hu G. Biological functions and clinical significance of the newly identified long noncoding RNA RP185F18.6 in colorectal cancer. Oncol Rep. 2018;40(5):2648-2658. [CrossRef]
21. Wang WJ, Chen D, Jiang MZ, et al. Downregulation of gasdermin D promotes gastric cancer proliferation by regulating cell cycle-related proteins. J Dig Dis. 2018;19(2):74-83. [CrossRef]
22. Privitera G, Rana N, Armuzzi A, Pizarro TT. The gasdermin protein family: emerging roles in gastrointestinal health and disease. Nat Rev Gastroenterol Hepatol. 2023;20(6):366-387. [CrossRef]
23. Hu R, Liang J, Ding L, et al. Gasdermin D inhibition ameliorates neutrophil mediated brain damage in acute ischemic stroke. Cell Death Discov. 2023;9(1):50. [CrossRef]
24. Silva CMS, Wanderley CWS, Veras FP, et al. Gasdermin-D activation by SARS-CoV-2 triggers NET and mediate COVID-19 immunopathology. Crit Care. 2022;26(1):206. [CrossRef]
25. Wang J, Yao J, Liu Y, Huang L. Targeting the gasdermin D as a strategy for ischemic stroke therapy. Biochem Pharmacol. 2021;188:114585. [CrossRef]
26. Ocal R, Buldukoglu OC, Hasoglan MG, Korucuk M, Cekin Y, Ocal S. Migraine and gasdermin D: a new perspective on the inflammatory basis of migraine. Acta Neurol Belg. 2024;124(3):981-986. [CrossRef]
27. Magro F, Sousa P, Ministro P. C-reactive protein in Crohn’s disease: how informative is it? Expert Rev Gastroenterol Hepatol. 2014;8(4):393-408. [CrossRef]