Children with Tourette's syndrome may suffer immunoglobulin A dysgammaglobulinemia: preliminary report

Abstract

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.

Figure 1

Plasma levels of total immunoglobulin (Ig)G (A), IgM (B), and IgA (C) in Tourette’s syndrome/obsessive-compulsive (TS/OCD) patients (n = 24) and age-matched healthy control subjects (n = 22). There were no differences in the levels of IgG and IgM between the patients and control children, but the levels of total IgA are significantly lower in the patients (*p = .02).

Figure 2

Plasma levels of immunoglobulin (Ig)A against myelin basic protein (MBP) (A), myelin-associated glycoprotein (MAG) (B), ganglioside GM1 (C), and lysoganglioside (D) are significantly lower in Tourette’s syndrome/obsessive-compulsive (TS/OCD) patients than in healthy age-matched control subjects (*p < .05), whereas the levels of anti-tubulin IgA do not differ (E).

Figure 3

Plasma levels of total immunoglobulin (Ig)A (A) and anti-myelin basic protein (MBP) IgA (B) in patients with history of pediatric autoimmune neuropsychiatric disorder associated with Streptococcus (PANDAS; n = 9) compared with non-PANDAS cases (n = 10) and healthy children (n = 22) shown as values in individual subjects, as well as mean ± SD (*p < .05). No differences were observed in anti-myelin-associated glycoprotein, ganglisoside, lysoganglioside, or tubulin IgA levels.