Lack of HLH in FMF

OpenAlex English

BACKGROUND: Macrophage 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-γ and IL-18 play crucial roles, with monocyte and macrophage hyperresponsiveness to IFN-γ 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-γ between sJIA/MAS and FMF patients. METHODS: Five sJIA/MAS and five FMF patients were included. PBMCs were stimulated in vitro with IFN-γ for 45 min. Levels of IFN-γ-induced chemokines CXCL9, CXCL10, and IL-18 in supernatants were measured using cytometric bead arrays before and after stimulation. RESULTS: PBMCs from MAS patients produced higher baseline CXCL9 levels compared to FMF patients in a flare, with differences increasing post-IFN-γ stimulation. IFN-γ stimulation also upregulated IL-18 production in MAS patients but not in FMF patients. CONCLUSION: Enhanced responsiveness to IFN-γ distinguishes sJIA/MAS from FMF patients, which may explain the lower occurrence of MAS in FMF.