RATIONALE: PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) is a clinical entity with diagnostic criteria of prepubertal onset of symptoms, sudden onset or episodic course of symptoms, and temporal association of neuropsychiatric symptoms (tics, OCD, anxiety) with Group B Streptococcal infection. The pathogenesis of PANDAS remains controversial. We present a case of specific antibody deficiency to Str. Pneumoniae, with IgG2/IgG4 deficiency, whose clinical features include PANDAS like symptoms temporally associated with sinopulmonary infections.CASE HISTORY: 10 yo male developed neuropsychiatric symptoms (facial tic, psychogenic cough) after having Pneumonia in January, 2002, and was suspected of having PANDAS based on his clinical features and elevated ASO/anti-DNAse B Antibody titers in 2003. Despite antibiosis (Azithromycin and Amoxicillin-Clavulanate), the patient had recurrent sinopulmonary infections that correlated to the frequency and severity of behavioral symptoms.RESULTS: Conventional immune workup revealed low IgG2/IgG4 levels, suboptimal response to Pneumovax, and rapid decline of Pneumococcal Antibody titers. His peripheral blood mononuclear cells and peripheral blood derived macrophages produced low levels of proinflammatory cytokines (TNF-α, IL-6, IL1-β, and IL-12p40) in response to lipopolysaccharide, without TLR4 polymorphisms (Asp299Gly and Thr399lle). IVIG (0.6 g/kg/dose q3weeks) was started and there was nearly complete resolution of sinopulmonary infections and PANDAS like symptoms. Behavioral symptoms often reappear two to five days prior to next IVIG infusion.CONCLUSIONS: PANDAS symptoms may not be solely associated with Streptococcal infections, but could be related to other microbial infection in the presence of dysregulated inflammatory/immune responses and, in such conditions, IVIG may reveal superior therapeutic effects over antibiosis. RATIONALE: PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) is a clinical entity with diagnostic criteria of prepubertal onset of symptoms, sudden onset or episodic course of symptoms, and temporal association of neuropsychiatric symptoms (tics, OCD, anxiety) with Group B Streptococcal infection. The pathogenesis of PANDAS remains controversial. We present a case of specific antibody deficiency to Str. Pneumoniae, with IgG2/IgG4 deficiency, whose clinical features include PANDAS like symptoms temporally associated with sinopulmonary infections. CASE HISTORY: 10 yo male developed neuropsychiatric symptoms (facial tic, psychogenic cough) after having Pneumonia in January, 2002, and was suspected of having PANDAS based on his clinical features and elevated ASO/anti-DNAse B Antibody titers in 2003. Despite antibiosis (Azithromycin and Amoxicillin-Clavulanate), the patient had recurrent sinopulmonary infections that correlated to the frequency and severity of behavioral symptoms. RESULTS: Conventional immune workup revealed low IgG2/IgG4 levels, suboptimal response to Pneumovax, and rapid decline of Pneumococcal Antibody titers. His peripheral blood mononuclear cells and peripheral blood derived macrophages produced low levels of proinflammatory cytokines (TNF-α, IL-6, IL1-β, and IL-12p40) in response to lipopolysaccharide, without TLR4 polymorphisms (Asp299Gly and Thr399lle). IVIG (0.6 g/kg/dose q3weeks) was started and there was nearly complete resolution of sinopulmonary infections and PANDAS like symptoms. Behavioral symptoms often reappear two to five days prior to next IVIG infusion. CONCLUSIONS: PANDAS symptoms may not be solely associated with Streptococcal infections, but could be related to other microbial infection in the presence of dysregulated inflammatory/immune responses and, in such conditions, IVIG may reveal superior therapeutic effects over antibiosis.