Soluble IL-2 receptor levels in patients with Graves'ophthalmopathy

Prummel, Mark F.; Wiersinga, W. M.; Gaag, R van der; Mourits, Maarten P.; Koornneef, L.

doi:10.1111/j.1365-2249.1992.tb06462.x

Cited by 31 publications

(10 citation statements)

References 24 publications

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“…Changes in serum cytokines have been also observed in GO. In patients with elevated sIL‐2R a better response to corticosteroid therapy was observed [15], and IL‐6, CD30 and TNF‐α receptor I had some value for predicting a therapeutic outcome of orbital irradiation [16]. In our study no significant relationship was found for any measured parameter to the development and course of GO.…”

Section: Discussioncontrasting

confidence: 56%

The relationship between thyroid function, serum monokine induced by interferon gamma and soluble interleukin-2 receptor in thyroid autoimmune diseases

Jiskra

Antošová

Límanová

et al. 2009

Clinical and Experimental Immunology

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SummaryInteractions between cytokines play an important role in the development of thyroid autoimmunity. Using enzyme-linked immunosorbent assay we investigated serum concentrations of soluble interleukin-2 receptor (sIL-2R), interferon-gamma, tumour necrosis factor (TNF)-a, interleukin (IL)-10, CD30, monokine induced by interferon-gamma (MIG), cytotoxic T lymphocyte antigen-4 and markers of apoptosis decoy receptor 3 and Bcl-2 in 28 patients with hyperthyroid Graves' disease (GD), 24 patients with untreated Hashimoto's thyroiditis (HT) and 15 healthy controls. TNF-a, IL-10 and sIL-2R were higher in GD compared with HT and controls (TNF-a: 8·79 in GD versus 2·54 pg/ml in HT, P = 0·01; IL-10: 10·00 versus 3·10 versus 3·10 pg/ ml, P1 < 0·001, P2 = 0·005; sIL-2R: 1·26 versus 0·64 versus 0·46 ng/ml, P < 0·001). MIG and CD30 were higher in HT compared with controls (649·22 Ϯ 262·55 versus 312·95 Ϯ 143·35 pg/ml, P = 0·037, 6·57 Ϯ 2·35 versus 3·03 Ϯ 1·04 U/ml, P = 0·036 respectively). In GD sIL-2R decreased when the euthyroid state was achieved (1·31 Ϯ 0·64 versus 0·260 Ϯ 0·11, n = 12, P < 0·001). sIL-2R correlated positively with free thyroxine (FT4) (R = 0·521, P = 0·000) and negatively with thyroid stimulating hormone (TSH) (R = -0·472, P = 0·00132). MIG correlated negatively with FT4 (R = -0·573, P = 0·00234) and positively with TSH (R = 0·462, P = 0·0179). The results suggest that serum concentrations of sIL-2R and MIG are related to thyroid function rather than to activation of autoimmunity.

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Section: Discussioncontrasting

confidence: 56%

The relationship between thyroid function, serum monokine induced by interferon gamma and soluble interleukin-2 receptor in thyroid autoimmune diseases

Jiskra

Antošová

Límanová

et al. 2009

Clinical and Experimental Immunology

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“…Although these levels failed to correlate with disease activity or severity, those individuals with the highest levels exhibited enlarged extraocular muscles. 87 Serum concentrations of IL-6 and soluble IL-6R were found to be elevated in GD compared to healthy individuals. 88 These were even higher in the subset with active TAO.…”

Section: Cytokinesmentioning

confidence: 90%

“…85 Messenger RNA encoding cytokines, including TNFa, IL-1b, IFNc, IL-4, IL-6, and IL-10, was detected in extraocular muscle and fat from patients with TAO. 86 Prummel et al 87 found elevated serum soluble IL-2R (sIL-2R) levels in approximately 45% of individuals with TAO. Although these levels failed to correlate with disease activity or severity, those individuals with the highest levels exhibited enlarged extraocular muscles.…”

Section: Cytokinesmentioning

confidence: 99%

Current Concepts in the Molecular Pathogenesis of Thyroid-Associated Ophthalmopathy

Wang¹,

Smith²

2014

Invest. Ophthalmol. Vis. Sci.

198

156

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Graves' disease (GD) is a common autoimmune condition. At its core, stimulatory autoantibodies are directed at the thyroid-stimulating hormone receptor (TSHR), resulting in dysregulated thyroid gland activity and growth. Closely associated with GD is the ocular condition known as thyroid-associated ophthalmopathy (TAO). The pathogenesis of TAO remains enigmatic as do the connections between the thyroid and orbit. This review highlights the putative molecular mechanisms involved in TAO and suggests how these insights provide future directions for identifying therapeutic targets. Genetic, epigenetic, and environmental factors have been suggested as contributory to the development of GD and TAO. Thyroid-stimulating hormone receptor and insulin-like growth factor receptor (IGF-1R) are expressed at higher levels in the orbital connective tissue from individuals with TAO than in healthy tissues. Together, they form a functional complex and appear to promote signaling relevant to GD and TAO. Orbital fibroblasts display an array of cell surface receptors and generate a host of inflammatory molecules that may participate in T and B cell infiltration. Recently, a population of orbital fibroblasts has been putatively traced to bone marrow-derived progenitor cells, known as fibrocytes, as they express CD45, CD34, CXCR4, collagen I, functional TSHR, and thyroglobulin (Tg). Fibrocytes become more numerous in GD and we believe traffic to the orbit in TAO. Numerous attempts at developing complete animal models of GD have been largely unsuccessful, because they lack fidelity with the ocular manifestations seen in TAO. Better understanding of the pathogenesis of TAO and development of improved animal models should greatly accelerate the identification of medical therapy for this vexing medical problem.

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“…Nonetheless, if there is a cross-reactive antigen in both thyroid and eye muscle, blood-borne T cells might be expected to respond to such an antigen, as thyroid antigen-specific T cells can be identified (albeit at low level) in the circulation, particularly after removal of the non-specific suppressor infiuence of the CD8'*' subset [17,20,21]. Furthermore, an increase in soluble IL-2 receptor levels and a decrease in CD8'^ T cell numbers can be detected in the circulation of patients with severe TAO [22,23], indicating that the ostensibly localized process in ophthalmopathy can produce detectable effects in the blood.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, an increase in soluble IL-2 receptor levels and a decrease in CD8'^ T cell numbers can be detected in the circulation of patients with severe TAO [22,23], indicating that the ostensibly localized process in ophthalmopathy can produce detectable effects in the blood.…”

Section: Discussionmentioning

confidence: 99%

T cell responses to orbital antigens in thyroid-associated ophthalmopathy

Arnold

Tandon

McIntosh

et al. 1994

Clinical and Experimental Immunology

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SUMMARYThyroid-associated ophthalmopathy (TAO) is most likely to be a T cell-mediated disease, in which cytokines released in the extraocular muscles activate fibroblasts, increasing glycosaminoglycan production. The nature of the orbital antigen recognized by the infiltrating T cells is unclear, although it is possible that there is cross-reactivity between this and a thyroid autoantigen to explain the close association with thyroid autoimmunity. We have tested the ability of human and porcine eye muscle antigen preparations to stimulate proliferation of circulating T cells from healthy subjects and patients with TAO or Graves' disease without clinical TAO. Occasional responses were seen, particularly after depletion of CD8"^ T cells, and two out of 10 TAO patients responded to eye muscle proteins of 25-50 kD after fractionation of antigens on gels and subsequent elution. There was no disease-specific response ofT cells to Rl, R14, Dl and 1D3, recombinant proteins identified from screening an eye muscle cDNA library with sera from patients with autoimmune thyroid disease. We have also found that interferon-gamma (IFN-7) production by T cells from TAO patients was not stimulated by eye muscle membrane antigens or by 1D3. These results suggest that the frequency of circulating T cells responding to eye muscle antigens in TAO is low, and that several candidate orbital antigens, including the 64-kD protein 1D3, are unlikely to be important T cell autoantigens in this condition.

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Soluble IL-2 receptor levels in patients with Graves'ophthalmopathy

Cited by 31 publications

References 24 publications

The relationship between thyroid function, serum monokine induced by interferon gamma and soluble interleukin-2 receptor in thyroid autoimmune diseases

The relationship between thyroid function, serum monokine induced by interferon gamma and soluble interleukin-2 receptor in thyroid autoimmune diseases

Current Concepts in the Molecular Pathogenesis of Thyroid-Associated Ophthalmopathy

T cell responses to orbital antigens in thyroid-associated ophthalmopathy

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