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

Harvey Singer, Colin Gause, Christina Morris, Pablo Lopez

Research output: Contribution to journalArticle

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 an- tineuronal 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 lysoganglio- side 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.

Original languageEnglish (US)
Pages (from-to)1198-1205
Number of pages8
JournalPediatrics
Volume121
Issue number6
DOIs
StatePublished - Jun 2008

Fingerprint

Streptococcal Infections
Biomarkers
Antibodies
Cytokines
Enzyme-Linked Immunosorbent Assay
Antigens
Putamen
Prefrontal Cortex
Serum
Autoimmunity
Western Blotting
Prospective Studies
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections
Brain
Proteins

Keywords

  • Antineuronal antibodies
  • Cytokines
  • Longitudinal analysis
  • Lysoganglioside GM1
  • PANDAS

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Serial immune markers do not correlate with clinical exacerbations in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. / Singer, Harvey; Gause, Colin; Morris, Christina; Lopez, Pablo.

In: Pediatrics, Vol. 121, No. 6, 06.2008, p. 1198-1205.

Research output: Contribution to journalArticle

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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 an- tineuronal 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 lysoganglio- side 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.",
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