TSH‐R expression and cytokine profile in orbital tissue of active <i>vs.</i> inactive Graves’ ophthalmopathy patients

Wakelkamp, I. M. M. J.; Bakker, O.; Baldeschi, Lelio; Wiersinga, Wilmar M.; Prummel, Mark F.

doi:10.1046/j.1365-2265.2003.01708.x

Cited by 204 publications

(127 citation statements)

References 42 publications

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“…The increased expression of IL-12 mRNA in thyroid and orbital fat tissues has been reported in GD and in active GO, respectively [24,25]. Furthermore, IL-12 is involved in the development of animal model of autoimmune thyroid disorders [38].…”

Section: Discussionmentioning

confidence: 99%

“…Increased serum levels of IL-12 have been reported in GD [21][22][23]. Furthermore, IL-12B mRNA expression has been demonstrated in thyroid tissues from patients with GD [24] and in orbital fat tissues from patients with active GO [25], but not in extraocular muscle tissues (EOM), or EOM-derived T cell lines from patients with GO undergoing corrective strabismus surgery [26]. Numerous single nucleotide polymorphisms (SNP) have recently been identified in the IL-12B gene [27] and the 1188A/C polymorphism in the 3' untranslated region (3'UTR) of the IL-12B gene is associated with IL-12B mRNA expression levels [28] and IL-12 secretion levels from lipopolysaccharide (LPS) and purified protein derivative (PPD) stimulated peripheral blood mononuclear lymphocytes (PBML) [29].…”

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confidence: 95%

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Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

et al. 2006

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Abstract. Graves' disease (GD) is an autoimmune disorder with genetic predisposition and frequently associated with Graves' ophthalmopathy (GO). Interleukin 12 (IL-12) is an important mediator of inflammatory immune responses and is expressed in the thyroid and orbit. IL-12B gene, which encodes the p40 subunit of IL-12, is located at chromosome 5q31-33. The aim of the present study was to investigate whether IL-12B gene polymorphism is associated with the development of GD or GO. IL-12B gene polymorphism was studied in Japanese GD patients (n = 329) and healthy control subjects without anti-thyroid autoantibodies or a family history of autoimmune disorders (n = 226). The A/C polymorphism at position 1188 of the 3' untranslated region (3'UTR) of the IL-12B gene was analyzed using the polymerase chain reaction -restriction fragment length polymorphism method. There was no difference in allele or genotype frequency of the IL-12B gene polymorphism (1188A/C) between GD patients and control subjects. There was no association of the IL-12B gene polymorphism with ophthalmopathy, severity of hyperthyroidism or serum IgE levels. There was no association of the IL-12B gene polymorphism with serum IL-12 levels, which were significantly elevated in hyperthyroid phase of GD. In conclusion, IL-12B gene 1188A/C polymorphism is not associated with GD or GO susceptibility in Japanese.

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Section: Discussionmentioning

confidence: 99%

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confidence: 95%

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

et al. 2006

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“…16 This concept is further supported by the finding of a positive correlation between GO patients' TSHR mRNA levels in orbital adipose tissues excised during decompression surgery and the patients' clinical activity score. 17 Similarly, TSHR appears to be more abundant in pretibial dermopathy than in normal pretibial skin. 9 A relationship between adipogenesis and TSHR expression appears also to be present in cultures of orbital preadipocyte fibroblasts undergoing in vitro differentiation.…”

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confidence: 97%

Pathogenesis of Graves Ophthalmopathy: Implications for Prediction, Prevention, and Treatment

Garrity

Bahn

2006

American Journal of Ophthalmology

212

151

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PURPOSE-To review current concepts regarding the pathogenesis of Graves ophthalmopathy (GO). We have presented this information in the context of potential target sites for novel disease therapies. DESIGN-Review of recent literature. METHODS-Synthesis of recent literature.RESULTS-Enlargement of the extraocular muscle bodies and expansion of the orbital fatty connective tissues is apparent in patients with GO. These changes result from abnormal hyaluronic acid accumulation and edema within these tissues and expanded volume of the orbital adipose tissues. Recent studies have suggested that the increase in orbital fat volume is caused by stimulation of adipogenesis within these tissues. The orbital fibroblast appears to be the major target cell of the autoimmune process in GO. A subset of these cells is capable of producing hyaluronic acid and differentiating into mature adipocytes, given appropriate stimulation. In addition, orbital fibroblasts from patients with GO have been shown to display immunoregulatory molecules and to express both thyrotropin receptors (TSHRs) and insulin-like growth factor 1 receptors (IGF-1Rs). Increased TSHR expression in the GO orbit appears to be the result of stimulated adipocyte differentiation. The activation of IGF-1R on orbital fibroblasts by immunoglobulins from GO patients results in increased production of both hyaluronic acid and molecules that stimulate the infiltration of activated T cells into areas of inflammation.

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“…Although the presence of significantly higher levels of IL-2 are reported in the patients with GO, 39 the gene polymorphisms of this cytokine have not been investigated in GO. We did not find a significant association between GO and IL-2 -330T/G or 166G/T polymorphisms.…”

Section: Discussionmentioning

confidence: 99%

“…38,39 The presence of IL-12 is necessary for induction of T-helper1 response. The IL-12 À1188A/C polymorphism has been examined in immune-mediated diseases, 40,41 and may alter the susceptibility to a number of autoimmune diseases such as multiple sclerosis and type I diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

Genetic susceptibility to Graves’ ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes

Anvari

Khalilzadeh

Esteghamati

et al. 2009

Eye

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TSH‐R expression and cytokine profile in orbital tissue of active vs. inactive Graves’ ophthalmopathy patients

Cited by 204 publications

References 42 publications

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

Interleukin-12B Gene Polymorphism does not Confer Susceptibility to Graves' Ophthalmopathy in Japanese Population

Pathogenesis of Graves Ophthalmopathy: Implications for Prediction, Prevention, and Treatment

Genetic susceptibility to Graves’ ophthalmopathy: the role of polymorphisms in proinflammatory cytokine genes

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