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


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.
Division of Pediatric Neurology, Johns Hopkins Hospital, Rubenstein Child Health Building, Suite 2158, 200 N Wolfe St, Baltimore, MD 21287, USA. hsinger@jhmi.edu
Harvey S
HS
Singer
Colin
C
Gause
Christina
C
Morris
Pablo
P
Lopez
D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology* / Q000382:microbiology*; D015415:Biomarkers / Q000097:blood; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000097:blood / Q000276:immunology* / Q000382:microbiology*; D009422:Nervous System Diseases / Q000097:blood / Q000276:immunology* / Q000382:microbiology*; D011446:Prospective Studies; D012720:Severity of Illness Index; D013290:Streptococcal Infections / Q000097:blood / Q000150:complications* / Q000276:immunology*
D015415:Biomarkers