Mouse models of systemic juvenile idiopathic arthritis and macrophage activation syndrome

Area of Science:

• Pediatric Rheumatology
• Immunology
• Animal Modeling

Background:

• Macrophage activation syndrome (MAS) is a life-threatening condition complicating pediatric rheumatic diseases, particularly systemic juvenile idiopathic arthritis (SJIA).
• Current treatments for SJIA, including biologics, do not fully address refractory disease and recurrent MAS.
• The pathophysiology of MAS, though phenotypically similar to hemophagocytic lymphohistiocytosis (HLH), remains incompletely understood.

Purpose of the Study:

• To review existing animal models of SJIA and MAS.
• To evaluate how these models reflect the clinical and pathological features of SJIA and MAS.
• To identify knowledge gaps and future research directions for MAS and SJIA animal models.

Main Methods:

• Literature review of published animal models relevant to SJIA and MAS.
• Analysis of the strengths and limitations of each model in recapitulating disease aspects.
• Discussion of insights gained from these models regarding disease mechanisms.

Main Results:

• No single animal model perfectly replicates MAS, but several capture key aspects of SJIA and/or MAS.
• Existing models provide valuable insights into the pathophysiology of these conditions.
• Models highlight the complexity and heterogeneity of MAS and SJIA.

Conclusions:

• Animal models are essential tools for dissecting the complex pathophysiology of SJIA and MAS.
• Further development and utilization of refined animal models are needed.
• These models hold promise for identifying novel therapeutic targets and strategies for refractory SJIA-MAS.