The implications of “thyroid-growth-immunoglobulins” (TGI) for the understanding of sporadic nontoxic nodular goitre

Doniach, Deborah; Chiovato, Luca; Hanafusa, Toshiaki; Bottazzo, Gian Franco

doi:10.1007/bf01857429

Cited by 10 publications

(2 citation statements)

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“…Growth effects could be demonstrated in goitrous Graves' disease, and in some 'simple' goitres. Negative results were obtained with Igs from most normal subjects and more significantly from patients with large goitres of known non-autoimmune aetiology (Doniach et al, 1982). The thyroid growth CBA is not at present a quantitative assay and it was essential to confirm the findings with a better established and technically less demanding method.…”

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confidence: 99%

DETECTION OF THYROID GROWTH IMMUNOGLOBULINS (TGI) BY [³H]‐THYMIDINE INCORPORATION IN CULTURED RAT THYROID FOLLICLES

Chiovato

Hammond

Hanafusa

et al. 1983

Clinical Endocrinology

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A new bioassay is described for detecting the growth stimulating immunoglobulins (TGI) that contribute to goitre formation in human thyroid autoimmune diseases. It measures the incorporation of tritiated thymidine into intact rat thyroid follicles grown in tissue culture. This radiometric assay demands much less technical skill than the cytochemical bioassays (CBA) previously employed. It has good reproducibility and the techniques and apparatus are available in many clinical laboratories. Immunoglobulins (Igs) from 68% of patients with goitrous Graves' disease were positive, in proportion with goitre size, and this showed no correlation with T3 levels, or three accepted methods for conventional thyroid stimulating antibodies. Non-toxic nodular goitre cases gave positive results in 3/9 who had recurrences after one or more thyroidectomies and in 1/10 cases of familial simple goitre. All normal subjects and all endemic goitre cases were negative as well as 21 cases of sporadic non-toxic nodular goitre. Although it is less sensitive than the 'growth CBA' it clearly emphasizes the essential difference between the intensity of growth stimulus which leads to the regular hyperplasia of thyroid epithelium seen in Graves' thyrotoxicosis and the disorganized and metabolically uncoordinated hyperplasia typical of non-toxic nodular goitre.

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confidence: 99%

DETECTION OF THYROID GROWTH IMMUNOGLOBULINS (TGI) BY [³H]‐THYMIDINE INCORPORATION IN CULTURED RAT THYROID FOLLICLES

Chiovato

Hammond

Hanafusa

et al. 1983

Clinical Endocrinology

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“…These include antibodies with thyroid growth [27] or thyrotropin-receptor bloclung [28] activities; some of the latter block thyroid growth in utero [29]. The description of these antibodies as well as monoclonal raised against the receptor will help better understand receptor structure and function [30].…”

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The thyroid “microsomal” antigen is an epitope on the thyrotropin receptor

Islam

Tuppal

Hawe

et al. 1986

J of Cellular Biochemistry

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Antimicrosomal antibodies are present in the sera of most patients with autoimmune thyroiditis, and Graves' disease. It has, in general, been difficult to separate antimicrosomal activity from that directed against the thyrotropin (TSH) receptor in Graves' IgG preparations. The "microsomal" antigen has been localized to the endoplasmic reticulum and microfollicular aspect of thyrocytes; its structure is however unknown. In an attempt to identify the thyroid microsomal antigen, we studied the interaction of Hashimoto's IgG with high microsomal antibody titre and negative for thyroglobulin with purified thyroid plasma and light microsomal membranes. We allowed Hashimoto's, Graves', and control IgGs to bind to protein blots of thyroid plasma membranes resolved on SDS-PAGE under non-reducing conditions. All seven Hashimoto's IgG at a concentration of 2 mg/ml interacted with an M approximately 197,000 polypeptide corresponding to the TSH holoreceptor. By contrast to Graves' IgG (which were positive at 1 mg/ml), however, this binding was not blocked by pretreatment of the protein blots with TSH. Normal IgGs showed no binding at concentrations of up to 2 mg/ml. Both Hashimoto's and Graves' IgG interacted with TSH-affinity column-purified receptor preparations. Two of the Hashimoto's IgGs induced adenylate cyclase activation in thyroid plasma membranes, three inhibited TSH-stimulated enzyme activation, and two were without effect. Two classes of autoantibodies, other than TSH receptor directed, were encountered; one class raised to antigens common to all seven patients and another class unique to individual patients, eg, Mr 210,000 and Mr 20,000 polypeptides. We propose that the TSH receptor has multiple epitopes (functional domains), and the one to which antimicrosomal antibody bind is likely to be spatially separated from that with which Graves' IgG and TSH interact. Differences in affinity or number of sites allows for the demonstration of Graves' IgG against a background of antimicrosomal antibody.

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The Heterogeneity of Autoimmune Responses

Feldmann

Doniach

Bottazzo

1985

Immunology of Rheumatic Diseases

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The implications of “thyroid-growth-immunoglobulins” (TGI) for the understanding of sporadic nontoxic nodular goitre

Cited by 10 publications

References 29 publications

DETECTION OF THYROID GROWTH IMMUNOGLOBULINS (TGI) BY [³H]‐THYMIDINE INCORPORATION IN CULTURED RAT THYROID FOLLICLES

DETECTION OF THYROID GROWTH IMMUNOGLOBULINS (TGI) BY [³H]‐THYMIDINE INCORPORATION IN CULTURED RAT THYROID FOLLICLES

The thyroid “microsomal” antigen is an epitope on the thyrotropin receptor

The Heterogeneity of Autoimmune Responses

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The implications of “thyroid-growth-immunoglobulins” (TGI) for the understanding of sporadic nontoxic nodular goitre

Cited by 10 publications

References 29 publications

DETECTION OF THYROID GROWTH IMMUNOGLOBULINS (TGI) BY [3H]‐THYMIDINE INCORPORATION IN CULTURED RAT THYROID FOLLICLES

DETECTION OF THYROID GROWTH IMMUNOGLOBULINS (TGI) BY [3H]‐THYMIDINE INCORPORATION IN CULTURED RAT THYROID FOLLICLES

The thyroid “microsomal” antigen is an epitope on the thyrotropin receptor

The Heterogeneity of Autoimmune Responses

Contact Info

Product

Resources

About

DETECTION OF THYROID GROWTH IMMUNOGLOBULINS (TGI) BY [³H]‐THYMIDINE INCORPORATION IN CULTURED RAT THYROID FOLLICLES

DETECTION OF THYROID GROWTH IMMUNOGLOBULINS (TGI) BY [³H]‐THYMIDINE INCORPORATION IN CULTURED RAT THYROID FOLLICLES