Elsevier

Biological Psychiatry

Volume 67, Issue 7, 1 April 2010, Pages 679-683
Biological Psychiatry

Archival Report
Children with Tourette's Syndrome May Suffer Immunoglobulin A Dysgammaglobulinemia: Preliminary Report

https://doi.org/10.1016/j.biopsych.2009.09.034Get rights and content

Background

Postinfectious autoimmunity has been implicated in Tourette's syndrome and obsessive-compulsive disorder (TS/OCD), whereas increased frequency of upper respiratory tract infections (URTI) in TS/OCD patients suggests immune deficiency. We hypothesized that antineuronal antibodies may be elevated in patients (reflecting autoimmune processes), and levels of total immunoglobulins (Igs) may be decreased (reflecting immune deficiency).

Methods

We analyzed plasma of TS/OCD patients (n = 24) and healthy age- and sex-matched control subjects (n = 22) by enzyme-linked immunosorbent assay (ELISA) for the levels of total and specific IgG, IgM, and IgA against antigens previously identified in multiple sclerosis (myelin basic protein and myelin-associated glycoprotein) and Sydenham's chorea (ganglioside-GM1, lysoganglioside, and tubulin).

Results

Total IgA was decreased in TS/OCD patients (median 115 mg/100 mL) compared with control subjects (141 mg/100 mL; p = .02). Specific IgA against all antigens, except tubulin were also decreased in the patients (MPB 0 vs. 13 [ELISA units [EU]; myelin-associated glycoprotein 29 vs. 44 EU, p = .04; ganglioside GM1 21 vs. 35 EU, p = .01; lysoganglioside 44 vs. 56 EU, p = .03; tubulin 44 vs. 44 EU, p = .8). The levels of total IgA and anti-myelin basic protein (MBP) IgA were significantly lower in the subgroup of pediatric autoimmune neuropsychiatric disorder associated with Streptococcus (PANDAS) cases (n = 10) than in non-PANDAS cases (n = 9; total IgA 98 mg/100 mL vs. 133 mg/mL, p = .03; anti-MBP IgA 1 vs. 6 EU, p = .03) or healthy control subjects (total IgA 141 mg/100 mL, p = .02; anti-MBP IgA 13 EU, p = .005).

Conclusions

At least some TS/OCD patients may suffer IgA dysgammaglobulinemia, possibly rendering the children more prone to URTI.

Section snippets

Subjects

Blood samples of TS/OCD (n = 24, Table 1) and healthy age-matched control subjects (n = 22, Table 1) were collected as part of three clinical studies to perform pilot investigations of immune system in TS/OCD. The Human Investigation Committee at Yale University approved these studies; all parents signed a permission statement, and each child signed a statement of informed assent. Clinical evaluation was performed as described previously using ordinal severity scales of the Yale Global Tic

Plasma Levels of Total Ig Isotypes

TS/OCD patients had significantly lower levels of total plasma IgA (median 115 mg/100 mL, IQR 86–151) than the age-matched control subjects (141 mg/100 mL, IQR 121–170 in control subjects; U = 145; n1 = 24, n2 = 22, p = .02), although there were no differences in total IgG (935 mg/100 mL, IQR 746–1064 in patients vs. 977 mg/mL, IQR 803–1332 in control subjects, U = 200; p = .32) or total IgM levels (199 mg/mL, IQR 152–259 in patients vs. 209 mg/100 mL, IQR 148–240 in control subjects, U = 232; p

Discussion

TS/OCD patients have decreased total and specific IgA plasma levels in comparison with healthy age-matched children (Figures 1 and 2). This could contribute to deviation of immune responses in TS/OCD patients by at least two mechanisms. First, inhibitory functions of IgA in plasma on immune responses may be reduced (16), which could increase the vulnerability of TS/OCD patients for developing autoimmune disorders (17). Second, IgA secretion on mucosal surfaces may be affected (18, 19), and in

References (27)

  • L.A. Snider et al.

    PANDAS: Current status and directions for research

    Mol Psychiatry

    (2004)
  • A.J. Church et al.

    Anti-basal ganglia antibodies: A possible diagnostic utility in idiopathic movement disorders?

    Arch Dis Child

    (2004)
  • C.A. Kirvan et al.

    Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea

    Nat Med

    (2003)
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