Cumulating evidence has shown that PANS is associated with inflammation, dysregulation of immune cells, and importantly for this proposal, autoimmunity. Key inhibitors of autoimmunity are regulatory T cells (Tregs), a specialized population of T cells that maintain immune homeostasis and play an essential anti-inflammatory role by suppressing the inflammatory immune responses mediated by T helper cells and other immune cells. Previous research of children with early-onset OCD showed a dysregulation of circulating Tregs, giving evidence for the role of altered Treg function in PANS. Dr. Hussein’s prior study measured the amount of circulating Tregs in the peripheral blood of 11 children in PANS (flare and remission) and 11 healthy controls (HCs); initial results showed an increase in Tregs cells in peripheral blood of patients of PANS flare patients compared to HCs and a decrease in these cells in paired samples after PANS remission. The percentage of CD39+ cells (a marker of highly active and immunosuppressive Tregs) was also significantly higher in PANS flare compared to HCs and PANS remission.
Dr. Hussein hypothesizes that the CD39+ Treg subset in PANS flare is immunosuppressive and may have dysregulated response to signals that regulate trafficking to the brain. To test these, she will 1) determine the immunosuppression activity of CD39+ Treg during PANS flare and remission by measuring CD39 ATPase functional enzymatic activity, doing immunosuppression assays, and by measuring the Tregs- related anti-inflammatory immunosuppressive molecules (cytokines); and 2) evaluate the migratory capacity of Tregs in PANS by measuring expression levels of cytokine receptors that regulate Treg migration and by doing migration inhibition assays. Functional stability of Tregs will be analyzed by DNA demethylation epigenetic studies. Characterizing the role of CD39+Treg in PANS will lay the groundwork for a potential new PANS therapy, by either replacing faulty Tregs or enhancing functional ones.