Biography
Biography: Isaac Melamed
Abstract
Statement of the Problem: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a broad diagnostic criterion characterized by a severe, sudden onset of neuropsychiatric changes. Recently, we acquired evidence that other infectious pathogens (eg, Mycoplasma pneumoniae, Epstein-Barr virus; and Borrelia burgdorferi) may play a role in a similar neuroinflammatory syndrome. Innate immunity is the first line of defense against pathogens and is comprised of effectors that provide rapid, robust, non-specifi c responses. Two aspects of innate immunity are toll-like receptors (TLRs) and the complement
system. C1 esterase inhibitor (C1-INH) is the major inhibitor of the classical pathway. Recently, we explored the role of C1INH in a subset of patients with common variable immunodeficiencies (CVID) as well as the role of mast cell (MC) activation, which may lead to microglial activation and may function as a partner to TLR and C1INH signaling in developing neuroinflammation. In this study, we explored whether TLR-3 signaling, C1INH function, and MC activation play a role in the pathogenesis of post-infectious neurological diseases.
Methodology & Theoretical Orientation: We reviewed clinical cases of patients who presented with neurocognitive changes and had evidence of neuro-inflammation based on autoimmune, neurological biomarkers such as anti-68kDa, anti-GAD antibody autoimmune panels. Patients with neurocognitive clinical presentations and positive biomarkers had an immune
workup that included TLR signaling, C1INH levels, and atopic markers including MC signals.
Findings: Th e response to poly (I:C), the synthetic analogue dsRNA (TLR 3), was decreased by 86±8% compared to normal control. Average levels of C1INH were 16+2 mg/dL, while control levels were 22+5. All patients had evidence of atopy based on IgE, RAST tests, and MC activation.
Conclusion & Significance: We suggest that a complex of immune dysfunction, including TLR-3 signaling, C1INH levels, and atopic partners, specifically mast cell activation, are playing a crucial role in a neuro-inflammatory clinical presentation similar to PANS syndrome.