Caspase-1 Activity, IL-1beta, and IL-18 in Patients With FMF

NCT ID: NCT06981520

Last Updated: 2025-05-20

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-07-10
• Study Completion Date: 2026-01-19

Brief Summary

This study aims to investigate the intestinal mucosal expression of key inflammatory markers, namely Interleukin-1 (IL-1), Interleukin-18 (IL-18), and Caspase-1, in patients with Familial Mediterranean Fever (FMF). FMF is an autoinflammatory disorder characterized by recurrent episodes of fever and serosal inflammation. Recent studies suggest a possible role of intestinal immune activation in the disease pathogenesis, particularly through inflammasome-related cytokines. To better understand mucosal involvement in FMF, immunohistochemical staining for IL-1, IL-18, and Caspase-1 will be performed on intestinal biopsy samples obtained during routine endoscopic procedures. The staining intensity and distribution patterns will be evaluated and compared with age- and sex-matched healthy controls. The findings may help clarify mucosal inflammatory pathways involved in FMF and provide insight into novel therapeutic targets.

Detailed Description

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent episodes of fever, serositis, and elevated acute-phase reactants. The underlying pathophysiology involves mutations in the MEFV gene, which encodes pyrin, a protein involved in the regulation of the inflammasome complex. Aberrant inflammasome activation has been associated with increased production of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β) and interleukin-18 (IL-18), mediated through caspase-1 cleavage.

Although FMF primarily affects serosal surfaces, emerging evidence suggests that intestinal mucosal inflammation may also play a role in disease pathogenesis, possibly contributing to atypical symptoms such as abdominal pain, diarrhea, or subclinical intestinal involvement. However, the extent and nature of this mucosal immune activation remain largely unexplored.

This study is designed to evaluate the expression of IL-1, IL-18, and Caspase-1 in intestinal mucosal biopsy specimens obtained from FMF patients during routine endoscopic evaluation. Immunohistochemical staining techniques will be applied to assess the localization and intensity of these markers. The results will be compared to a control group of age- and sex-matched individuals undergoing endoscopy for non-inflammatory indications (e.g., functional gastrointestinal disorders) and without histopathologic mucosal abnormalities.

Staining will be semi-quantitatively scored by two independent pathologists blinded to clinical data. Correlations between cytokine expression levels and clinical characteristics of FMF (e.g., disease duration, mutation status, attack frequency, colchicine response) will also be explored.

This study aims to provide insights into the role of mucosal inflammasome activity in FMF, potentially identifying novel biomarkers or therapeutic targets. By characterizing intestinal expression of key inflammasome-related cytokines, we hope to expand current understanding of FMF pathophysiology beyond classical serosal involvement.

Conditions

Familial Mediterranean Fever; Intestinal Disease; Genetic Disease; Fever

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: OTHER

Study Groups

Grup 1: Group Title: FMF Patients Group/Cohort Label: FMF

1\. FMF Patients (Group/Cohort Description) Patients diagnosed with Familial Mediterranean Fever (FMF) according to clinical criteria and/or genetic analysis. Intestinal mucosal biopsy samples were obtained during routine endoscopy, and immunohistochemical staining for IL-1, IL-18, and Caspase-1 was performed.

No interventions assigned to this group

Grup 2: Group Title: Healthy Controls Group/Cohort Label: Control

2\. Healthy Controls (Group/Cohort Description) Healthy individuals without any known inflammatory or autoimmune disease, undergoing endoscopy for non-inflammatory indications such as functional gastrointestinal symptoms. Mucosal biopsy samples were collected and analyzed immunohistochemically for IL-1, IL-18, and Caspase-1 expression.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

Confirmed diagnosis of Familial Mediterranean Fever (FMF) according to Tel-Hashomer clinical criteria and/or MEFV gene mutation analysis (for FMF group)

Undergoing routine endoscopy with mucosal biopsy sampling

Availability of sufficient formalin-fixed paraffin-embedded (FFPE) tissue for immunohistochemical analysis

For controls: absence of systemic inflammatory or autoimmune disease -

Exclusion Criteria

Current use of immunosuppressive therapy (excluding colchicine)

Severe infection, active malignancy, or other systemic disease affecting intestinal mucosa

Inadequate biopsy specimen quality for histopathological evaluation

-

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hitit University

OTHER

Sponsor Role: lead

Responsible Party

Mustafa Sahin

Principal Investigator, Associate Professor of Medical Biochemistry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mustafa Şahin, Assoc.Prof

Role: PRINCIPAL_INVESTIGATOR

Hitit University Faculty of Medicine, Turkey

Locations

Hitit University Erol Olçok Training and Research Hospital

Çorum, , Turkey (Türkiye)

Countries

Turkey (Türkiye)

Central Contacts

Mustafa Şahin, Assoc.Prof

Role: CONTACT

sahinmustafa@hitit.edu.tr

+90 364 219 30 00 ext. 2722

Facility Contacts

Mustafa Şahin, Assoc. Prof.

Role: primary

mustafaistanbulx@hotmail.com

+90 364 219 30 00 ext. 2722

Other Identifiers

2025/37

Identifier Type: OTHER

Identifier Source: secondary_id

Hitit University, Çorum

Identifier Type: -

Identifier Source: org_study_id