Author(s)
Deeptha Bejugam, BS
Jasmine Gulati, MAPP
Veranca Shah, BS
Brent Harris MD, PhD
Earl H. Harley, MD FAAP FACS
Affiliation(s)
Georgetown University School of Medicine; Department of Otolaryngology - Head and Neck Surgery, Medstar Georgetown University Hospital ;
Abstract:
Educational Objective: At the conclusion of this presentation, the participants should be able to identify key markers (IL-17A, FoxP3+) in PANDAS, explain their role in neuroinflammation, and discuss potential therapies like secukinumab and the role of ENTs in PANDAS diagnosis and management.
Objectives: PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) is a condition characterized by sudden onset neuropsychiatric symptoms in children following streptococcal infections, which are thought to trigger an autoimmune response. This study evaluates if PANDAS patients demonstrate a significantly different number of immune markers which may contribute to its pathogenesis and recurring flares.
Study Design: Prospective cohort study.
Methods: This study utilized immunohistochemistry (IHC) to analyze mucosa samples from 21 clinically diagnosed PANDAS patients and 6 controls who underwent tonsillectomy with or without adenoidectomy. Expression levels of CD3+, CD4+, CD25+, FoxP3+, IL-17A+, and RORyt+ markers, obtained as percentages of the total cells in the mucosa samples, were compared between the two groups.
Results: Median age of the PANDAS cohort was 10 years (IQR: 8-13.5) and 9 years (IQR: 7.5-9.75) for controls. Mann-Whitney tests for mucosa IHC data revealed statistically significant higher levels of cells with FoxP3+ (2.00% v 0.00%, p = 0.0166) and IL-17A+ (1.00% v. 0.00%, p = 0.04298) markers in PANDAS patients compared to controls. No significant differences were observed for CD3+, CD4+, CD25+, or RORyt+ markers between PANDAS and control groups.
Conclusions: The elevated levels of IL-17A and FoxP3+ cells in PANDAS patients align with recent literature emphasizing the role of Th17 lymphocytes and regulatory T (Treg) cells in PANDAS/PANS pathology. Increased IL-17A supports the hypothesis of persistent neuroinflammation, while elevated FoxP3+ expression may indicate a potentially dysregulated Treg response. These results highlight the need for further research into anti-IL-17A therapies, such as secukinumab, and their potential therapeutic benefits in managing PANDAS. These findings emphasize the role of an interdisciplinary approach that includes ENT-related and immunological interventions to manage and treat PANDAS effectively.