Bridging Autoimmunity and Hyperinflammation: Shared Immunological Pathways Among Autoimmune/Inflammatory Syndrome Induced by Adjuvants, Systemic Lupus Erythematosus, and Macrophage Activation Syndrome

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is characterized by immune dysregulation associated with exposure to exogenous substances with immunostimulatory properties, particularly in susceptible individuals. Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease characterized by loss of immune tolerance, autoantibody production, and immune complex deposition. Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory syndrome characterized by excessive activation of macrophages and T lymphocytes and may occur as a severe complication of SLE and other inflammatory conditions. This review explores the clinical and immunological overlap among ASIA, SLE, and MAS, with particular attention to the potential contribution of adjuvant-related exposures to immune activation in susceptible individuals. Shared and convergent immunological pathways, including activation of innate and adaptive immunity, loss of immune tolerance, macrophage activation, and dysregulation of cytokine networks involving IL-1β, IL-6, IL-17, IL-18, TNF-α, and interferon-γ, are discussed. Rather than representing an established causal or sequential pathway, the relationship among these conditions is considered within a conceptual framework based on overlapping immunological mechanisms. Clinically, overlapping manifestations among ASIA, SLE, and MAS may pose diagnostic challenges and contribute to underrecognition or delayed treatment. Careful assessment of potential triggering exposures, integration of clinical and laboratory findings, and prompt recognition of hyperinflammatory manifestations are important for appropriate clinical management. This review highlights the need for further mechanistic and prospective studies to determine the clinical relevance of the immunological overlap among ASIA, SLE, and MAS, validate potential biomarkers, and evaluate targeted therapeutic strategies directed at shared inflammatory pathways.