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Lack of HLH in FMF

Ozge Basaran1, Erdal Sag1,2, Elif Arslanoglu Aydın3

  • 1Department of Pediatric Rheumatology, Hacettepe University, 06230, Altındag, Ankara, Turkey.

Pediatric Rheumatology Online Journal
|February 8, 2025
PubMed
Abstract

Insights

Macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis (sJIA) involves heightened interferon-gamma (IFN-γ) responses. This enhanced IFN-γ responsiveness distinguishes MAS patients from Familial Mediterranean Fever (FMF) patients, potentially explaining why MAS is rare in FMF.

Area of Science:

  • Immunology
  • Rheumatology
  • Genetics

Background:

  • Macrophage activation syndrome (MAS) is a severe complication of systemic juvenile idiopathic arthritis (sJIA).
  • MAS involves excessive T cell and macrophage activation, leading to a cytokine storm with key roles for interferon-gamma (IFN-γ) and IL-18.
  • Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by recurrent fevers, but MAS is rare in FMF patients despite inflammation.

Purpose of the Study:

  • To compare the in vitro responsiveness of peripheral blood mononuclear cells (PBMCs) to IFN-γ between patients with sJIA/MAS and FMF.
  • To investigate the role of IFN-γ-induced chemokines and IL-18 in differentiating these conditions.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) were isolated from five sJIA/MAS patients and five FMF patients.
  • PBMCs were stimulated in vitro with IFN-γ.
  • Levels of IFN-γ-induced chemokines (CXCL9, CXCL10) and IL-18 were measured before and after stimulation using cytometric bead arrays.

Main Results:

  • PBMCs from MAS patients exhibited higher baseline CXCL9 levels compared to FMF patients during a flare.
  • IFN-γ stimulation significantly increased CXCL9 levels in MAS patients compared to FMF patients.
  • IFN-γ stimulation upregulated IL-18 production in MAS patients but not in FMF patients.

Conclusions:

  • Enhanced in vitro responsiveness to IFN-γ is a distinguishing feature of sJIA/MAS patients compared to FMF patients.
  • This heightened IFN-γ sensitivity in MAS may contribute to the lower incidence of MAS in FMF.
  • Understanding these differential responses could inform therapeutic strategies for MAS.
Keywords:
CXCL-10CXCL-9Familial Mediterranean feverIL-18Macrophage activation syndrome

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