Lack of HLH in FMF

BAŞARAN H. Ö., SAĞ E., Aydin E. A., Aydin B., Tasdemir N. K., Celikel E., ...More

PEDIATRIC RHEUMATOLOGY, no.1, 2025 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2025
  • Doi Number: 10.1186/s12969-025-01064-9
  • Journal Name: PEDIATRIC RHEUMATOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, MEDLINE, Directory of Open Access Journals
  • Hacettepe University Affiliated: Yes

Abstract

BackgroundMacrophage activation syndrome (MAS) is a severe complication of systemic juvenile idiopathic arthritis (sJIA), driven by excessive activation of T cells and macrophages, resulting in a cytokine storm. IFN-gamma and IL-18 play crucial roles, with monocyte and macrophage hyperresponsiveness to IFN-gamma amplifying MAS-related inflammation. Familial Mediterranean Fever (FMF), an autosomal recessive disease, is characterized by recurrent fever episodes due to MEFV gene mutations. Despite intense inflammation in FMF, MAS is rare. This study aimed to compare in vitro responsiveness of peripheral blood mononuclear cells (PBMCs) to IFN-gamma between sJIA/MAS and FMF patients.MethodsFive sJIA/MAS and five FMF patients were included. PBMCs were stimulated in vitro with IFN-gamma for 45 min. Levels of IFN-gamma-induced chemokines CXCL9, CXCL10, and IL-18 in supernatants were measured using cytometric bead arrays before and after stimulation.ResultsPBMCs from MAS patients produced higher baseline CXCL9 levels compared to FMF patients in a flare, with differences increasing post-IFN-gamma stimulation. IFN-gamma stimulation also upregulated IL-18 production in MAS patients but not in FMF patients.ConclusionEnhanced responsiveness to IFN-gamma distinguishes sJIA/MAS from FMF patients, which may explain the lower occurrence of MAS in FMF.