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


Avar Aydın P. Ö., Yaz İ., İnan D., Özçakar Z. B., Oskay Halaçlı S., Çağdaş Ayvaz D. N.

TURKISH JOURNAL OF PEDIATRICS, vol.67, no.3, pp.361-371, 2025 (SCI-Expanded, Scopus, TRDizin) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 67 Issue: 3
  • Publication Date: 2025
  • Doi Number: 10.24953/turkjpediatr.2025.5389
  • Journal Name: TURKISH JOURNAL OF PEDIATRICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CAB Abstracts, Veterinary Science Database, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.361-371
  • Hacettepe University Affiliated: Yes

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.