Serum ADAM8, ADAM10, and ADAM17 levels in attack-free familial Mediterranean fever patients: A cross-sectional case-control study

Abstract

Aim: Familial Mediterranean Fever (FMF) is a monogenic autoinflammatory disease characterized by recurrent inflammatory attacks and persistent subclinical inflammation. The role of the ADAM (a disintegrin and metalloproteinase) family of metalloproteinases in FMF pathogenesis remains unclear. This study aimed to compare serum levels of ADAM8, ADAM10, and ADAM17 between FMF patients during attack-free periods and healthy controls and evaluate their associations with inflammatory markers.

Materials and Methods: This single-center, cross-sectional, case–control study included 36 FMF patients and 36 age and sex-matched healthy controls. All patients received regular colchicine therapy, and blood samples were collected during attack-free periods. Serum levels of ADAM8, ADAM10, and ADAM17 were measured by ELISA. Acute-phase reactants [C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen] were analyzed using routine laboratory methods. Between-group comparisons, correlation analyses, multivariable binary logistic regression analyses, and receiver operating characteristic (ROC) analyses were performed.

Results: Serum ADAM8 and ADAM10 levels were significantly higher in FMF patients than in controls (p<0.001), whereas ADAM17 levels did not differ between groups. ADAM10 showed weak-to-moderate positive correlations with CRP and fibrinogen, while ADAM8 and ADAM17 exhibited limited associations with inflammatory markers. ROC analysis demonstrated moderate discriminatory performance for ADAM8 and ADAM10; however, these findings should be interpreted as exploratory due to the cross-sectional design and potential confounding factors.

Conclusion: Serum ADAM8 and ADAM10 levels were higher in clinically attack-free FMF patients than in healthy controls. In multivariable analyses adjusted for age, sex, body mass index, and smoking status, ADAM8 and ADAM10 remained independently associated with FMF, whereas ADAM17 did not. These findings should be interpreted cautiously and may reflect the chronic/subclinical inflammatory burden of FMF rather than disease-specific pathogenic mechanisms. Furthermore, larger longitudinal studies are needed.