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

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.

Inclusion criteria

Age 18 years or older

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

History of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)

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

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