Advancing Our Understanding of IVIg in Pediatric Acute-Onset Neuropsychiatric Syndrome

Intravenous immunoglobulin (IVIg) is a pooled product containing polyclonal IgG collected from the plasma of thousands of healthy donors. Originally developed as a replacement therapy for patients with humoral immunodeficiencies, IVIg has since been widely adopted in the treatment of several autoimmune and inflammatory conditions, owing to its extensive immunomodulatory and anti-inflammatory effects. IVIg exerts a wide range of actions by influencing multiple components of both the innate and adaptive immune systems. These include modulation of Fcγ receptor expression and function, inhibition of complement activation, neutralization of autoantibodies, regulation of cytokine networks, control of pro-inflammatory monocytes, and regulation of multiple immune cells, also through epigenetic modulation. Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) represents one of the most complex conditions in pediatric neuropsychiatry, involving the basal ganglia and characterized by a broad range of abrupt-onset neuropsychiatric symptoms, irrespective of the underlying infectious trigger. Recent clinical and translational studies indicate that IVIg can attenuate neuropsychiatric symptoms and restore immune balance in children with PANS. Randomized trials have produced variable results. Converging clinical and mechanistic evidence supports the potential therapeutic value of IVIg in selected patients with moderate-to-severe or relapsing disease. In this overview, we examine current data on IVIg use in PANS, emphasizing its immunological rationale, emerging clinical benefits, and the need for biomarker-guided studies to better identify responders and optimize treatment outcomes.