PANDAS

How does repeated Streptococcus pyogenes infection induce rapid onset of neuropsychiatric symptoms in children?

Activated microglia in the olfactory bulb after multiple GAS infections

Despite emerging evidence that inflammatory molecules (e.g. cytokines and complement) alter synapse formation, neuronal connectivity and behavior, the molecular mechanisms underlying impairment of brain development and function by infections that induce an aberrant immune response remain poorly understood.

Group A Streptococci (S. pyogenes; GAS), the primary agent for acute pharyngitis in children, is associated with several autoimmune diseases, including the central nervous system (CNS) autoimmune motor and behavioral disorders Sydenham’s chorea and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). Recurrent GAS mucosal infections induce a strong antigen-specific Th17 cellular response in mice and humans. Th17 cells have been implicated in many autoimmune diseases including multiple sclerosis, where they trigger inflammation and destruction of the blood-brain barrier (BBB).

Our preliminary experiments show that these T cells specifically home to the brain, localizing primarily in the olfactory bulb (OB) and along the olfactory nerve as well as some other brain regions where OB neurons send projections and eventually make synaptic connections. We are investigating the mechanisms of how these T cells induce neuronal damage and BBB breakdown and the consequences for behavioral outcomes.

Related publications

Current projects

Human genetic studies aimed at understanding and treating pediatric autoimmune disease

PANDAS Autoantibodies in the Blood Brain Barrier

Mechanisms of CNS infiltration by immune cells following S. pyogenes infection

Videos

Research from Dr. Agalliu’s laboratory in the Department of Neurology at Columbia University Irving Medical Center has recently shown that the olfactory route can be used as gateway to the CNS by immune cells in an animal model. (PANDAS Network)
Pat Cleary and Dritan Agalliu discuss their collaboration to investigate the link between the generation of GAS-specific Th17 cells and CNS autoimmunity. (Journal of Clinical Investigation)

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Our research on PANDAS is made possible by donations to the lab’s PANDAS Research Fund.