Archival ReportChildren with Tourette's Syndrome May Suffer Immunoglobulin A Dysgammaglobulinemia: Preliminary Report
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)
- et al.
Neuronal surface glycolytic enzymes are autoantigen targets in post-streptococcal autoimmune CNS disease
J Neuroimmunol
(2006) - et al.
Identification of pyruvate kinase as an antigen associated with Tourette's syndrome
J Neuroimmunol
(2006) - et al.
Antibody-mediated neuronal cell signaling in behavior and movement disorders
J Neuroimmunol
(2006) - et al.
Increased serum levels of interleukin-12 and tumor necrosis factor-alpha in Tourette's syndrome
Biol Psychiatry
(2005) - et al.
Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with Tourette's syndrome: A preliminary study
Biol Psychiatry
(2007) - et al.
Neuropsychiatric disorders associated with streptococcal infection: A Case-control study among privately insured children
J Am Acad Child Adolesc Psychiatry
(2008) - et al.
Antibodies to neuron-specific antigens in children with autism: Possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A
J Neuroimmunol
(2002) - et al.
Immunology of TS/OCD
J Am Acad Child Adolesc Psychiatry
(1997) - et al.
Human serum IgA downregulates the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6) in human monocytes
Blood
(1994) - et al.
Mycoplasma pneumoniae infection and Tourette's syndrome
Psychiatry Res
(2004)
PANDAS: Current status and directions for research
Mol Psychiatry
Anti-basal ganglia antibodies: A possible diagnostic utility in idiopathic movement disorders?
Arch Dis Child
Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea
Nat Med
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2016, Brain, Behavior, and ImmunityCitation Excerpt :Elevated inflammatory microglial markers in the striatum, including Iba1, have been documented in TS, post-mortem (Lennington et al., 2014; Hong et al., 2004; Morer et al., 2010) and in a recent PET imaging study (Kumar et al., 2014). Alterations in peripheral immune markers (Kawikova et al., 2010, 2007; Leckman et al., 2005; Matz et al., 2012) and the response to inflammatory challenge (Servello et al., 2011; Weidinger et al., 2014) have also been described. These observations suggest a ‘two-hit’ model of inflammatory dysregulation.
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2015, Brain ResearchCitation Excerpt :Despite the variability in anti-HCN4 serum levels across TS patients, their correlation with clinical severity was not investigated; also, there was no evidence of coexisting systemic inflammation in TS patients with anti-HCN4 antibodies. Also using denaturing techniques, both Kawikova et al. (2010) and Morris-Berry et al. (2013) failed to show raised serum titers of antibodies against antigens hypothesized to be relevant in putative post-streptococcal disorders (SC and PANDAS), including the GAS carbohydrate antigen N-acetyl-glucosamine, the surface brain lysoganglioside GM1, and the cytoskeletal protein tubulin. Live cell systems expressing candidate self-antigens in their natural conformational state on the cell surface (e.g. neuroblastoma or animal brain-derived live cell lines, or transfected cell lines like human embryonic kidney cells [HEK]) are a preferable methodological platform to study autoantibody reactivity relevant in vivo, and have contributed to the discovery of highly relevant autoantibody species in neuropsychiatry (Lancaster and Dalmau, 2012; Irani and Vincent, 2012).