Elsevier

Pediatric Neurology

Volume 28, Issue 2, February 2003, Pages 119-125
Pediatric Neurology

Original article
Antistreptococcal, neuronal, and nuclear antibodies in Tourette syndrome

https://doi.org/10.1016/S0887-8994(02)00507-6Get rights and content

Abstract

Previous studies have suggested associations between Tourette syndrome and attention-deficit–hyperactivity disorder and antistreptococcal antibodies and between Tourette syndrome and antinuclear antibodies. In this study, antistreptolysin O, antideoxyribonuclease B, antinuclear, and antineuronal antibodies were measured in 41 children with Tourette syndrome and 38 controls, selected without regard to history of streptococcal infection. Results revealed that mean antistreptococcal titers did not differ between diagnostic groups. In addition, multiple regression analysis was unable to predict antistreptococcal antibody titers according to age and diagnosis. The frequency of elevated antistreptolysin O titers, based on a cutoff of 1:240, was significantly higher (P = 0.04) in patients with attention-deficit–hyperactivity disorder (64%) than in the group without attention-deficit–hyperactivity disorder (34%) but not when dichotomized according to age-matched normal values. No analysis of antideoxyribonuclease B titers identified any differences between groups. Antinuclear antibody titers were at least 1:160 in three of 33 Tourette syndrome patients; only one subject manifested a homogeneous staining pattern. Multiple regression analyses were unable to predict antinuclear, antineuronal, or anti-HTB-10 antibody titers according to the combination of age, diagnosis, and antistreptococcal titer. We suggest that longitudinal rather than single-point-in-time laboratory measurements be evaluated before definitive conclusions are drawn on associations between the diagnosis of Tourette syndrome, attention-deficit–hyperactivity disorder, or obsessive-compulsive disorders and antistreptococcal or antinuclear antibody titers.

Introduction

Streptococcal infection, through an immune-based mechanism, has recently been theorized to contribute to the exacerbation of tics, obsessive-compulsive symptoms, and attention-deficit–hyperactivity disorder (ADHD). In 1998, Swedo et al. [1] described a cohort with the sudden or explosive onset of tics and obsessive-compulsive behaviors as having a temporal association with streptococcal infection. This proposal has in turn led investigators to look for correlations between neuropsychiatric disorders and antistreptococcal and antineuronal antibody titers. Several studies using single-point-in-time measurements have revealed higher mean antistreptolysin O (ASO) titers in patients with Tourette syndrome compared with controls [2], [3], [4]. In one, ASO titers correlated with tic severity [4]. Other investigators, however, have revealed no association between antistreptococcal antibodies and TS [5], [6], [7], but in one report, a correlation was identified with the diagnosis of ADHD [6].

Antineuronal antibodies have also been measured in individuals with TS, with elevated titers reported against human postmortem putamen and rat striatum [5], [7]. However, in these reports the presence of higher immunoreactivity did not correlate with ADHD or obsessive-compulsive behavior. Morshed and colleagues [7] have also suggested that elevated titers of antinuclear antibodies correlate with the diagnosis of Tourette’s Syndrome.

In the current study the findings of previous investigators are reassessed by measuring the following in children and adolescents with the diagnoses of Tourette syndrome, obsessive-compulsive behavior, and ADHD: (1) ASO and antideoxyribonuclease B (anti-DNAse B) titers; (2) antinuclear antibody titers; (3) levels of autoantibodies against human postmortem caudate, putamen, and globus pallidus; and (4) levels of autoantibodies against a neuroblastoma cell line (HTB-10). Previously in this cohort, elevated enzyme-linked immunosorbent assay (ELISA) optical density measurements against putamen were found, but no linear correlation between optical density values and ASO or anti-DNAse B levels was found, although more subjects with higher antistreptococcal titers were diagnosed with Tourette syndrome [5]. This report addresses the proposals that ASO, antiDNAse B, and antinuclear antibodies titers correlate with the neuropsychiatric diagnoses of Tourette syndrome, ADHD, and obsessive-compulsive behavior. Contrary to the reports of several investigators, these diagnoses are hypothesized not to predict single-point-in-time levels of antistreptococcal or antinuclear antibodies.

Section snippets

Subjects

Forty-one outpatients with Tourette syndrome (33 males, 8 females; age range, 7 to 17 years; mean, 11.3 years) were voluntary participants in this hospital-approved study. All fulfilled the diagnostic criteria for Tourette’s syndrome as defined by the Tourette Syndrome Classification Study Group [8]. Patients were not preselected on the basis of a streptococcal infection. Results from ELISA antineuronal antibody analyses from this group have been published [5], [9]. The mean age of tic onset

Mean antistreptococcal antibody titers

Table 1 presents the number of participating individuals in each diagnostic group and the number for whom ASO and anti-DNAse B titers were available. The mean and S.D. of ASO and anti-DNAse B titers in all nonoverlapping groups, which included all possible combinations of diagnostic comorbidity, are presented in Table 2. As shown in the table, no comparison of differences in antistreptococcal antibody titers between unique diagnostic groups produced significant Bonferroni/Dunn adjusted P

Discussion

Immune-based hypotheses have been proposed for some pediatric patients with tic disorders, obsessive-compulsive behavior, and ADHD. Using a postulated role of group A β-hemolytic streptococcal infection, researchers have sought to identify whether individuals with these problems manifest increased levels of antistreptococcal antibodies. In two studies, adults with Tourette syndrome were manifested higher ASO and anti-DNAse B titers than age-matched controls, but there was no association between

Acknowledgements

Supported in part by grants from the National Institutes of Health (5R01NS37706-02) and the National Tourette Syndrome Association.

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