Change in Gasdermin-D gene expression in familial Mediterranean fever compared to healthy children with or without acute infections

Abstract

Background. Gasdermin-D (GSDMD) is an inflammasome regulator. Pyroptosis and GSDMD-mediated interleukin (IL)-1β secretion abolish in GSDMD-deficient familial Mediterranean fever (FMF) knock-in mice. We aimed to investigate GSDMD gene expression (GSDMD-∆), acute phase reactants (APRs), serum IL-1β, and IL-18 levels in FMF patients during attacks and attack-free periods. Methods. We tested GSDMD-∆, serum APRs, and serum IL-1β and IL-18 in 16 FMF patients (G1), during attack (G1-V1) and at attack-free visits (G1-V2). The GSDMD-∆, serum IL-1β and IL-18 were measured in febrile controls with acute infections (G2) and healthy children (G3). Results. Age and sex distribution of patients and controls were similar. Median GSDMD-∆ was 10 times higher in G1-V1 compared to G1-V2 (p0.05). GSDMD-∆ in G1 strongly correlated with serum C-reactive protein and amyloid-A (r>0.60, p0.05). Conclusion. We showed a significantly increased GSDMD-∆ for the first time in humans, thereby indicating the distinct role of GSDMD-∆ as a biomarker similar to APRs in FMF attacks. It was even higher than levels detected during acute infections, supporting the functional involvement of GSDMD-∆ in FMF attacks. GSDMD-∆ correlated with APRs but not with serum IL-1β and IL-18 levels.

Keywords

• Familial Mediterranean fever
• gasdermins
• MEFV
• infection