Thyroid-stimulating antibody activity between different immunoglobulin G subclasses.

Weetman, A P; Yateman, M; Ealey, P. A.; Black, C M; Reimer, Charles B.; Williams, R; Shine, Brian; Marshall, Nicholas J.

doi:10.1172/jci114768

Cited by 130 publications

(64 citation statements)

References 25 publications

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“…It has been reported that the thyroid-stimulating antibody is IgG 1 [18]. Our previous data that serum IL-10 increases in patients with intractable GD [14] appears to be consistent with this report because IL-10 is also a switching factor for IgG [12,13].…”

Section: Discussionsupporting

confidence: 90%

Ratio of Serum IgG3 to Total IgG Concentration and Goiter Size Are Independent Factors in Intractability of Graves' Disease

et al. 2007

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Abstract. Peripheral immunoglobulin (Ig) G 3 -secreting cells and serum concentrations of interleukin (IL)-10, a classswitching factor to IgG 3 -secreting cells, increase in patients with intractable Graves' disease (GD). However, they are not practical for laboratory tests. To find more stable and easily detectable markers of disease intractability or disease severity in patients with GD or Hashimoto's disease (HD), we examined the serum concentration of IgG 3 in 58 euthyroid GD patients who had been undergoing antithyroid drug treatment for more than 5 years but still must continue drug treatment to maintain a euthyroid state (intractable GD), 26 GD patients who had maintained a euthyroid state for more than 2 years without any treatment (GD in remission), 20 untreated, thyrotoxic GD patients, 40 euthyroid HD patients treated with thyroxine (5 men and 35 women), 13 untreated, euthyroid HD patients, and 39 healthy volunteers. Serum concentrations of IgG 3 increased in euthyroid patients with intractable GD and in those with GD in remission, but serum concentrations of IgG were not altered. The ratio of serum concentrations of IgG 3 to total IgG (IgG 3 /IgG ratio) was higher in euthyroid patients with intractable GD than in those with GD in remission. Multiple logistic-regression analysis demonstrated that IgG 3 /IgG ratio and goiter size were independent factors in disease intractability of GD patients. These results suggest that IgG 3 /IgG ratio and goiter size may be used as independent markers associated with GD intractability.

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Section: Discussionsupporting

confidence: 90%

Ratio of Serum IgG3 to Total IgG Concentration and Goiter Size Are Independent Factors in Intractability of Graves' Disease

et al. 2007

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“…These data reinforce the significance of the Th1 immune response in the pathogenesis of Graves' disease that we have previously proposed (3). Although our animal model may not perfectly mimic Graves' disease in humans, data supporting the involvement of the Th1 immune response in Graves' patients, for example, Th1-type TSAb (59), are indeed present. …”

Section: Discussionsupporting

confidence: 82%

Schistosoma mansoni and α-Galactosylceramide: Prophylactic Effect of Th1 Immune Suppression in a Mouse Model of Graves’ Hyperthyroidism

Nagayama¹,

Watanabe

Níwa³

et al. 2004

The Journal of Immunology

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Graves’ hyperthyroidism, an organ-specific autoimmune disease mediated by stimulatory thyrotropin receptor (TSHR) autoantibodies, has been considered a Th2-dominant disease. However, recent data with mouse Graves’ models are conflicting. For example, we recently demonstrated that injection of BALB/c mice with adenovirus coding the TSHR induced Graves’ hyperthyroidism characterized by mixed Th1 and Th2 immune responses against the TSHR, and that transient coexpression of the Th2 cytokine IL-4 by adenovirus skewed Ag-specific immune response toward Th2 and suppressed disease induction. To gain further insight into the relationship between immune polarization and Graves’ disease, we evaluated the effect of Th2 immune polarization by helminth Schistosoma mansoni infection and α-galactosylceramide (α-GalCer), both known to bias the systemic immune response to Th2, on Graves’ disease. S. mansoni infection first induced mixed Th1 and Th2 immune responses to soluble worm Ags, followed by a Th2 response to soluble egg Ags. Prior infection with S. mansoni suppressed the Th1-type anti-TSHR immune response, as demonstrated by impaired Ag-specific IFN-γ secretion of splenocytes and decreased titers of IgG2a subclass anti-TSHR Abs, and also prevented disease development. Similarly, α-GalCer suppressed Ag-specific splenocyte secretion of IFN-γ and prevented disease induction. However, once the anti-TSHR immune response was fully induced, S. mansoni or α-GalCer was ineffective in curing disease. These data support the Th1 theory in Graves’ disease and indicate that suppression of the Th1-type immune response at the time of Ag priming may be crucial for inhibiting the pathogenic anti-TSHR immune response.

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“…However, studies on cytokine profiles in thyroid tissues and sera provided controversial data regarding Th1 to Th2 balance [39]. Furthermore, of importance, TSAbs in human sera are of IgG1 subclass (Th1 type in humans) [40].…”

Section: Th1 Versus Th2 Immune Balance In Development Ofmentioning

confidence: 99%

Animal Models of Graves' Hyperthyroidism

Nagayama

2005

Endocr J

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Abstract. Graves' disease is a common organ-specific autoimmune disease characterized by overstimulation of the thyroid gland with agonistic anti-thyrotropin (TSH) receptor autoantibodies, which leads to hyperthyroidism and diffuse hyperplasia of the thyroid gland. Several groups including us have recently established several animal models of Graves' hyperthyroidism using novel immunization approaches, such as in vivo expression of the TSH receptor by injecting syngeneic living cells coexpressing the TSH receptor, the major histocompatibility complex (MHC) class II antigen and a costimulatory molecule, or genetic immunization using plasmid or adenovirus vectors coding the TSH receptor. This breakthrough has made it possible for us to study the pathogenesis of Graves' disease in more detail and has provided important insights into our understanding of disease pathogenesis. The important new findings that have emerged include: (i) the shed A subunit being the major autoantigen for TSAb, (ii) the significant role played by dendritic cells (DCs) as professional antigen-presenting cells in initiating disease development, (iii) contribution of MHC and particularly non-MHC genetic backgrounds in disease susceptibility, and (iv) influence of some particular infectious pathogens on disease development. However, the data regarding Th1/Th2 balance of TSH receptor-specific immune response or the association of Graves' hyperthyroidism with intrathyroidal lymphocytic infiltration are rather inconsistent. Future studies with these models will hopefully lead to better understanding of disease pathogenesis and help develop novel strategies for treatment and ultimately prevention of Graves' disease in humans.

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Thyroid-stimulating antibody activity between different immunoglobulin G subclasses.

Cited by 130 publications

References 25 publications

Ratio of Serum IgG3 to Total IgG Concentration and Goiter Size Are Independent Factors in Intractability of Graves' Disease

Ratio of Serum IgG3 to Total IgG Concentration and Goiter Size Are Independent Factors in Intractability of Graves' Disease

Schistosoma mansoni and α-Galactosylceramide: Prophylactic Effect of Th1 Immune Suppression in a Mouse Model of Graves’ Hyperthyroidism

Animal Models of Graves' Hyperthyroidism

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