Humoral Factors in Graves’ Ophthalmopathy

Toccafondi, R; Rotella, Carlo Maria; Zonefrati, Roberto; Tanini, Annalisa

doi:10.1007/978-1-4613-0945-1_12

Cited by 4 publications

(6 citation statements)

References 37 publications

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“…Fig. Previous attempts to search an autoantibody stimu¬ lating glycosaminoglycan synthesis in human skin fibroblasts have yielded conflicting results (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). As shown, there was no significant correlation between the two.…”

Section: Resultsmentioning

confidence: 99%

“…There was no significant correlation between the two aspects. Rotella and his associates reported the presence of a functional autoantibody which stimu¬ lates collagen synthesis in skin fibroblasts of Graves' disease patients with ophthalmopathy, but not in those of PTM (6)(7)(8)(9)(10)(11)(12). 7 compares the activity of PTM IgGs to stimulate 35S incorporation into proteogly¬ can with the TSAb activity in original serum.…”

Section: Resultsmentioning

confidence: 99%

“…However, attempts to show that the sera of PTM patients stimulate proteoglycan synthesis in human skin fibro¬ blasts in culture have yielded conflicting results (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). For example, Joliffe et al (4) and Cheung et al (5) reported that serum components of PTM patients could stimulate glycosaminoglycan synthesis in human skin fibroblasts in culture.…”

mentioning

confidence: 99%

“…For example, Joliffe et al (4) and Cheung et al (5) reported that serum components of PTM patients could stimulate glycosaminoglycan synthesis in human skin fibroblasts in culture. On the other hand, Rotella and his associates reported that the IgG of PTM patients stimu-lated glycosaminoglycan synthesis in rat thyroid cells but not in human skin fibroblasts, although they showed that PTM IgG stimulates collagen synthesis in human skin fibroblasts in culture (6)(7)(8)(9)(10)(11)(12). A recent report by Tao et al also showed that glycosaminoglycan synthesis in cultured human skin fibroblasts was not stimulated by the sera of PTM patients which contained autoantibodies capable of stimulating thyroid tissue (13).…”

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confidence: 99%

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Immunoglobulin G of patients with circumscribed pretibial myxedema of Graves' disease stimulates proteoglycan synthesis in human skin fibroblasts in culture

Shishiba

Imai²,

Odajima³

et al. 1992

Acta Endocrinologica

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nor ophthalmopathy. Human skin fibroblasts were incubated with the IgGs and labeled with [35S]sulfate. The medium and cell layer were separated and the proteoglycan was extracted. The 35S radioactivity in the proteoglycan fraction was measured. Compared with normal IgGs or with those of Graves' disease without PTM or ophthalmopathy, PTM IgGs significantly increased the incorporation of the 35S into the proteoglycan. The effect of PTM IgG was dose-dependent. As PTM IgG did not alter degradation of the 35S labeled proteoglycan, an increase in 35S incorporation reflects increased synthesis. The effect was mediated through a mechanism other than adenylate cyclase activation. The present study demonstrates the presence of an autoantibody in PTM IgG that stimulates proteoglycan production through human skin fibroblasts. This is not correlated with the thyroid stimulating antibody activity. It is suggested that the activity of this antibody leads to the development of PTM.Circumscribed pretibial myxedema (PTM) is a cutaneous complication occasionally associated with Graves' dis¬ ease. Histochemical examination of the biopsied speci¬ men showed the accumulation of hyaluronic acid and proteoglycan (1, 2). In a previous paper, we examined the proteoglycans extracted from the affected skin and found that a large amount of dermatan sulfate proteog¬ lycan had accumulated (3). It is widely accepted that fibroblasts are the source of hyaluronic acid and proteo¬ glycan synthesis, because skin fibroblasts actively syn¬ thesize both of them in culture. It is tempting to speculate that an autoantibody IgG produced in Graves' disease patients may stimulate skin fibroblasts to synthesize excess amounts of hyaluronic acid and proteoglycan.However, attempts to show that the sera of PTM patients stimulate proteoglycan synthesis in human skin fibro¬ blasts in culture have yielded conflicting results (3-13). For example, Joliffe et al. (4) and Cheung et al. (5) reported that serum components of PTM patients could stimulate glycosaminoglycan synthesis in human skin fibroblasts in culture. On the other hand, Rotella and his associates reported that the IgG of PTM patients stimu-lated glycosaminoglycan synthesis in rat thyroid cells but not in human skin fibroblasts, although they showed that PTM IgG stimulates collagen synthesis in human skin fibroblasts in culture (6-12). A recent report by Tao et al. also showed that glycosaminoglycan synthesis in cultured human skin fibroblasts was not stimulated by the sera of PTM patients which contained autoantibodies capable of stimulating thyroid tissue (13). We wondered if there was an antibody IgG in patients with PTM capable of stimulating proteoglycan synthesis in human skin fibroblasts in culture, but that the effect was masked either by serum-derived growth factors or by limitations of the methods employed. In the present study, we examined this aspect-no serum component other than IgG was included, except for bovine serum albumin (BSA)-employing the recently developed methods for proteoglycan...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Immunoglobulin G of patients with circumscribed pretibial myxedema of Graves' disease stimulates proteoglycan synthesis in human skin fibroblasts in culture

Shishiba

Imai²,

Odajima³

et al. 1992

Acta Endocrinologica

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“…On the other hand, the EM have unique features compared to other striated muscles including greater number of spindles, grea ter blood flow, more abundant nerve fibers [16] and a differ ent antigenic pattern. Although the presence of serum au toantibodies reactive with OCT antigen in TAO has been claimed [102][103][104][105], their titers do not correlate with the se verity of eye symptoms and they are not disease specific [103,105,106]. Thus their pathological role seems to be not important.…”

Section: Link Between the Thyroid And Emmentioning

confidence: 99%

The Ocular Muscle Cell Is a Target of the Immune System in Endocrine Ophthalmopathy

Kiljański

Nebes

Wall

1995

Int Arch Allergy Immunol

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The exact pathogenic mechanism of thyroid-associated ophthalmopathy (TAO) remains unclear, and extensive studies on this disorder have resulted in often conflicting data. Well-known technical difficulties including the limited access to orbital tissues from patients with active and early disease, lack of an animal model and poor reproducibility of some of the immunological techniques used are in part responsible for this confusing situation. Despite this there is considerable evidence for eye muscle (EM) tissue involvement in the autoimmune reactions of TAO. Although the primary EM antigen(s) recognized by immunocompetent cells and autoantibodies has not been definitely identified, some good candidates, among them a membrane antigen of 64 kD which is also expressed in the thyroid, have been partially characterized. While it is unclear which component of the autoimmune reaction against EM – humoral or cell mediated – plays the more important role, autoantibodies seem to be responsible at least in part for the clinical features of the eye disorder. On the other hand, the orbital connective tissue (OCT) cells, especially the fibroblasts surrounding the EM fibers, seem to be extremely sensitive to stimulation by cytokines and other soluble proteins and immunoglobulins released in the course of an immune reaction in the muscle cells. Fibroblasts secrete large amounts of glycosaminoglycans and also participate in maintaining the autoimmune reaction. It seems likely that the EM is the main and primary target of the orbital autoimmune process whereas inflammation of the OCT is probably secondary.

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Antibodies against striated muscle, connective tissue and nuclear antigens in patients with thyroid-associated ophthalmopathy: Should Graves’ disease be considered a collagen disorder?

Kiljański

Peele

Stachura

et al. 1997

J Endocrinol Invest

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The identity and subcellular localization of the principal extraocular muscle (EOM) antigens and prevalences of the corresponding serum autoantibodies in thyroid-associated ophthalmopathy (TAO) need to be clarified. We have used porcine eye muscle tissue, which expresses all autoantigens identified in human tissue, as substrate in an indirect immunofluorescence assay. Several different patterns of antibody binding to EOM tissue antigens were observed with sera from patients with TAO namely, membrane, cytoplasmic, interstitial (endomysial) and nuclear. Overall, sera from 75% of patients with TAO contained one or more antibodies reactive with EOM, compared to 32% of patients with Graves' hyperthyroidism, 38% with Hashimoto's thyroiditis, and 16% of normals. All sera which reacted with EOM membrane or cytoplasmic antigens also reacted with the same antigen(s) in other skeletal muscle, but not in the other tissues tested. Sera from 31% of patients with TAO, but only 7% of those with Hashimoto's thyroiditis, and no patient with Graves' hyperthyroidism without evident ophthalmopathy, contained antinuclear antibodies (ANA). The most common nuclear fluorescence pattern was the finely speckled type typically associated with anti-Sm or anti-RNP antibodies. Significant positive correlations in patients with TAO were found between (i) EOM dysfunction and ANA (ii) eye disease of < 1 yr duration and EOM membrane-reactive antibodies and (iii) eye disease of < 1 yr duration and interstitial (endomysial) tissue-reactive antibodies. Although patients with Graves' disease do not usually exhibit other signs or immunologic features of a generalized collagen disorder, the finding of high prevalences of ANA and anti-striated muscle antibodies and, less often, anti-connective tissue antibodies in patients with ophthalmopathy, is consistent with it being a collagen-like disorder of the striated muscle, connective tissue and the thyroid. The reason why the inflammatory process is mainly limited to these tissues is unclear although cross reaction of ANA with tissue specific proteins or increased expression of muscle and connective tissue antigens in the orbit and skin, are possibilities.

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Humoral Factors in Graves’ Ophthalmopathy

Cited by 4 publications

References 37 publications

Immunoglobulin G of patients with circumscribed pretibial myxedema of Graves' disease stimulates proteoglycan synthesis in human skin fibroblasts in culture

Immunoglobulin G of patients with circumscribed pretibial myxedema of Graves' disease stimulates proteoglycan synthesis in human skin fibroblasts in culture

The Ocular Muscle Cell Is a Target of the Immune System in Endocrine Ophthalmopathy

Antibodies against striated muscle, connective tissue and nuclear antigens in patients with thyroid-associated ophthalmopathy: Should Graves’ disease be considered a collagen disorder?

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