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Pediatrics. 2008 Jun;121(6):1198-205. doi: 10.1542/peds.2007-2658.

Serial immune markers do not correlate with clinical exacerbations in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.

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1
Division of Pediatric Neurology, Johns Hopkins Hospital, Rubenstein Child Health Building, Suite 2158, 200 N Wolfe St, Baltimore, MD 21287, USA. hsinger@jhmi.edu

Abstract

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 G(M1) 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.

PMID:
18519490
DOI:
10.1542/peds.2007-2658
[Indexed for MEDLINE]
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