P0349 Gasdermin D: A New Inflammatory Biomarker in Assessing Clinical Disease Activity in Crohn’s Disease
Authors: Buldukoglu O C , Ocal S , Atar G E , Kaya B , Isik M D , Aydin Tigli G , Akca S , Akbay Harmandar F , Cekin Y , Cekin A H 
Published: January 2025

Abstract

Background
Crohn’s disease (CD) is a progressive, destructive, inflammatory bowel disease. Despite new treatment options in form of biologic and small-molecule therapy, a significant portion of CD patients require surgical interventions during disease course.
Assessment of treatment response and disease activity is crucial in management of patients with CD. Gasdermin D (GSDMD) is a protein which belongs to the gasdermin protein family and plays a role in inflammatory cell death, pyroptosis. GSDMD activation has been shown to be related to inflammatory states in a variety of disorders, including inflammatory bowel diseases.
Given the role of GSDMD in inflammation, we hypothesized that serum GSDMD levels of patients with CD may be linked to disease activity; thereby revealing a potential new inflammatory serum marker for assessing disease severity in CD patients in a non-invasive manner.

Methods
This prospective study was carried out at Antalya Training and Research Hospital, Turkey, between September 2022 and June 2024. 61 CD patients were enrolled in the study.
Age, sex, body mass index (BMI), smoking status, time since CD diagnosis, treatment modality used at the time of enrollment, concurrent use of steroids, previous medical and surgical treatment history for CD, involvement site of CD (ileum only or ileocolonic involvement) and Harvey-Bradshaw Index (HBI) results were recorded at the day of blood sampling. Laboratory workout utilized in the study comprised WBC, ESR, CRP and GSDMD.

Results
Correlations between study parameters and GSDMD levels were investigated. GSDMD was found to be statistically significantly negatively correlated with age (r=-0.30, p=0.018). GSDMD was found to be statistically significantly positively correlated with CRP (r=0.26, p=0.041). Smoking was strongly correlated with increased GSDMD levels. Non-smokers (n=53) had a median serum GSDMD level of 3.03 ng/ml, compared to 8.29 in smokers (n=8) and this difference was statistically significant (p=0.001). GSDMD levels were found to be statistically significantly related to HBI (r=0.64, p=0.0001).
Independent variables affecting serum GSDMD levels were investigated with multivariate logistic regression analysis. GSDMD levels were independently correlated with age (ß: -0,15, p=0.029), CRP (ß: -0,19, p=0.01) and HBI (ß: 0,95, p=0.000) of the patients.

Conclusion
This study is a pioneer study in revealing utility of serum GSDMD as a potential biomarker of clinical disease activity in patients with CD. Future studies will not only reveal more on the value of this biomarker as a tracker of clinical disease course, but also pave the path for a new potential therapeutic target in this burdensome disorder for both the patient and the healthcare team.

References
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