ARTICLE |
Departments of a Neurology
b Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland
OBJECTIVE. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections is hypothesized to be a poststreptococcal autoimmune disorder. If clinical exacerbations are triggered by a streptococcal infection that activates cross-reacting antibodies against neuronal tissue or alters the production of cytokines, then a longitudinal analysis would be expected to identify a correlation between clinical symptoms and a change in autoimmune markers.
PATIENTS AND METHODS. Serial serum samples were available on 12 children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections participating in a prospective blinded study: 2 samples before an exacerbation point, 1 during the clinical exacerbation, and 2 after the exacerbation. Six subjects had a well-defined clinical exacerbation in association with a documented streptococcal infection, and 6 had a clinical exacerbation without an associated streptococcal infection. All of the serum samples were assayed for antibodies against human postmortem caudate, putamen, and prefrontal cortex; commercially prepared antigens; and complex sugars. Cytokines were measured by 2 different methodologies.
RESULTS. No correlation was identified between clinical exacerbations and autoimmune markers, including: enzyme-linked immunosorbent assay measures of antineuronal antibodies; Western immunoblotting with emphasis on brain region proteins located at 40, 45, and 60 kDa or their corresponding identified antigens; competitive inhibition enzyme-linked immunosorbent assay to evaluate lysoganglioside GM1 antibodies; and measures of inflammatory cytokines. No differences were identified between individuals with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections with or without exacerbations triggered by streptococcal infections.
CONCLUSIONS. The failure of immune markers to correlate with clinical exacerbations in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections raises serious concerns about the viability of autoimmunity as a pathophysiological mechanism in this disorder.
Key Words: PANDAS longitudinal analysis antineuronal antibodies cytokines lysoganglioside GM1
Abbreviations: PANDAS—pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections GABHS—group A β-hemolytic streptococci ELISA—enzyme-linked immunosorbent assay ExWS—exacerbation with streptococcal infection ExWOS—exacerbation without streptococcal infection BA10—Brodmann's area 10 PBS—phosphate-buffered saline Ig—immunoglobulin TBS-T—Tris-buffered saline containing 0.1% Tween 20 BSA—bovine serum albumin GlcNAc—N-acetyl-β-D-glucosamine Th—T-helper IL—interleukin TNF—tumor necrosis factor MCP—macrophage chemoattractant protein RANTES—regulated upon activation, normal T cell expressed and secreted AUC—area under the curve
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PANDAS: Two Studies of Clinical Exacerbations Journal Watch Pediatrics and Adolescent Medicine, July 23, 2008; 2008(723): 6 - 6. [Full Text] |
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