Infections with S. pyogenes (GAS) are associated with brain autoimmune disorders: Sydenham’s chorea (SC) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). Autoantibodies form when the immune system fails to recognize the body’s own cells and tissues as “self” and attacks healthy tissue. Autoantibodies that target neurons are found in acutely ill children with SC or PANDAS; however, how these autoantibodies cross the blood-brain barrier (BBB; a key component of protecting the brain from harmful materials) remain unclear.
Dr. Agalliu has found that GAS-specific immune cells in mice enter the brain, cause BBB breakdown, and allow circulating autoantibodies to enter the brain. First, this study by Dr. Agalliu and his team led to the publication of a research article that described in depth how antibodies related to Streptococcal infections cross the blood-brain barrier in autoimmune brain inflammation that leads to PANDAS and other autoimmune disorders, based on animal models such as mouse models. The article also suggests treatments for the neuroinflammation itself such as antibiotics, with outcomes for PANDAS being generally positive. Second, this study led to an article (currently a pre-print) that outlines support for the role of GAS-associated neuroinflammation in PANDAS/PANS specifically tied to interleukin-17A (IL-17A). IL-17A is released by the immune system in response to GAS infections, but was found to promote brain inflammation as it disrupts the blood-brain barrier. The study found that targeting and neutralizing IL-17A may aid in treating PANDAS/PANS.
Resulting Publications:
*Platt, M.P., Agalliu, D., & Cutforth, T. (2017). Hello from the other side: How antibodies circumvent the blood-brain barrier in autoimmune encephalitis. Frontiers in Immunology, 8(442). https://doi.org/10.3389/fimmu.2017.00442
*Wayne, C.R., Bremner, L., Faust, T.E., Durán-Laforet, V., Ampatey, N., Ho, S.J., Feinberg, P.A., Arvanitis, P., Ciric, B., Delaney, S.L., Vargas-Deming, W., Swedo, S., Menon, V., Schafer, D.P., Cutforth, T., & Agalliu, D. Distinct Th17 effector cytokines differentially promote microglial and blood-brain barrier inflammatory responses during post-infectious encephalitis. bioRxiv. https://doi.org/10.1101/2023.03.10.532135