Antithyroid Drugs Inhibit In Vivo HLA-DR Expression in Thyroid Follicular Cells in Graves' Disease

Thyroid ◽  
2001 ◽  
Vol 11 (6) ◽  
pp. 575-580 ◽  
Author(s):  
Denise Engelbrecht Zantut-Wittmann ◽  
Marcos Antonio Tambascia ◽  
Miriam Aparecida da Silva Trevisan ◽  
Glauce Aparecida Pinto ◽  
José Vassallo
Keyword(s):  
Antithyroid Drugs ◽  
Graves Disease ◽  
Follicular Cells ◽  
Hla Dr ◽  
Thyroid Follicular Cells

Expression of an intercellular adhesion molecule, ICAM-1, by human thyroid cells

1989 ◽  
Vol 122 (1) ◽  
pp. 185-NP ◽  
Author(s):  
A. P. Weetman ◽  
S. Cohen ◽  
M. W. Makgoba ◽  
L. K. Borysiewicz
Keyword(s):  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Human Thyroid ◽  
Accessory Cell ◽  
Graves Disease ◽  
Follicular Cells ◽  
Thyroid Cells ◽  
Hla Dr ◽  
Thyroid Follicular Cells

ABSTRACT Intercellular adhesion molecule-1 (ICAM-1), hitherto identified on activated B cells, macrophages, dendritic cells, endothelia and certain epithelial cells, serves as a ligand for the lymphocyte function-associated antigen-1 (LFA-1). ICAM-1 binding by LFA-1 enhances the efficiency of lymphocyte-target cell and lymphocyte-accessory cell interactions. We have investigated the in-vitro expression of ICAM-1 by cultured thyroid cells from five patients with Graves' disease using indirect immunofluorescence analysis, and found that 30 ± 11% (mean ± s.d.) of cells were ICAM-1 positive under basal conditions. The proportion of cells which were ICAM-1 positive and the amount of ICAM-1 per cell (assessed by fluorescence intensity) were both increased in all cases by the cytokines γ-interferon, interleukin-1 and tumour necrosis factor. Immunohistochemical analysis of frozen sections from thyroidectomy specimens demonstrated ICAM-1 on thyroid follicular cells in areas of lymphocytic infiltration in patients with Graves' disease (n = 2) or Hashimoto's thyroiditis (n = 2). ICAM-1 was not found in specimens from a patient with a toxic multinodular goitre or a patient with Graves' disease without focal lymphocytic accumulation. These results suggest that the thyroid epithelium may express ICAM-1 as well as major histocompatibility complex class II antigens, such as HLA-DR, in response to locally synthesized cytokines. The enhanced expression of ICAM-1 may render these cells more susceptible as targets for lymphocytemediated cytotoxicity, and together with HLA-DR antigen expression may increase the accessory cell capability of the thyroid follicular cells. Journal of Endocrinology (1989) 122, 185–191

scholarly journals Autoimmune and non-autoimmune thyroid diseases have different patterns of cellular HLA class II expression

1999 ◽  
Vol 117 (4) ◽  
pp. 161-164 ◽  
Author(s):  
Denise Engelbrecht Zantut-Wittmann ◽  
Luís Henrique Barbosa Boechat ◽  
Glauce Aparecida Pinto ◽  
Miriam Aparecida da Silva Trevisan ◽  
José Vassallo
Keyword(s):  
Multinodular Goiter ◽  
Class Ii ◽  
Hla Class Ii ◽  
Follicle Cells ◽  
Graves Disease ◽  
Follicular Cells ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Hla Dr ◽  
Thyroid Follicular Cells

CONTEXT: Surface HLA-DR antigen is usually only expressed by antigen-presenting cells (APC). In autoimmune thyroid disease, follicle cells function as APC, thus expressing HLA-DR. However, non-autoimmune thyroid diseases may also express surface class II antigens. OBJECTIVE: To evaluate the presence and pattern of HLA class II expression in autoimmune and non-autoimmune thyroid disorders. DESIGN: Retrospective: histopathological and immunohistochemical analysis. LOCATION: Referral center, university hospital. SAMPLE: Ten histologically normal thyroids, 11 Graves’ disease, 7 Hashimoto’s thyroiditis, 10 atoxic multinodular goiter and 3 toxic adenomas were analyzed by immunohistochemistry, using a monoclonal antibody anti-HLA-DR. MAIN MEASUREMENTS: The presence of these antigens in thyroid follicular cells and their relation to inflammatory infiltrate was evaluated. The pattern of HLA-DR expression in thyroid follicular cells was analyzed: membrane, cytoplasmic or both. RESULTS: Although HLA-DR antigens were sparsely present in one of the 8 normal thyroids, in 6 of the 9 atoxic multinodular goiter and in 2 of the 3 toxic adenomas a net positivity could be seen in large areas. In all 5 Hashimoto’s thyroiditis and in 7 of the 10 Graves’ disease cases. This expression occurred in follicle cells either in contact with inflammatory cells or not. In non-autoimmune thyroid disease, HLA-DR positivity was essentially cytoplasmic, whereas in Graves’ disease and Hashimoto thyroiditis it was mainly in cell membranes. CONCLUSIONS: It is suggested that the HLA class II expression on the surface of follicle cells could be related to auto-antigen presentation to the immune system by these cells, leading to inflammation.

c-myc Expression is associated with increased proliferation activity in thyroid follicular cells of Graves' disease as stimulated by autoantibodies

1996 ◽  
Vol 135 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Kenji Kashima ◽  
Shigeo Yokoyama ◽  
Tsutomu Daa ◽  
Kenji Takahashi ◽  
Iwao Nakayama ◽  
...  
Keyword(s):  
Lymphocytic Infiltration ◽  
Nuclear Antigen ◽  
Graves Disease ◽  
Thyrotropin Receptor ◽  
Follicular Cells ◽  
Hla Dr ◽  
Thyroid Follicular Cells ◽  
Proliferation Activity ◽  
Hyperplastic Change ◽  
Medical University

Kashima K, Yokoyama S, Daa T, Takahashi K, Nakayama I, Noguchi S. c-myc Expression is associated with increased proliferation activity in thyroid follicular cells of Graves' disease as stimulated by autoantibodies. Eur J Endocrinol 1996:135:69–76. ISSN 0804–4643 Expression on thyroid follicular cells of HLA-DR, c-myc protein and proliferating cell nuclear antigen (PCNA) was examined immunohistochemically in 28 cases of Graves' disease (GD) and in 29 cases of Hashimoto's thyroiditis (HT). Immunoreactivity for PCNA in GD was seen not only in follicular cells adjacent to a lymphocytic infiltration, where the follicular cells were positive for HLA-DR, but also in hyperplastic follicular cells without the infiltration. The distribution of expressed c-myc protein was similar to that of PCNA in GD but not in HT. Semiquantitatively graded degrees of lymphocytic infiltration and expression of HLA-DR, c-myc and PCNA in GD showed a high correlation with one another. However, the degrees of c-myc expression in HT showed no significant correlation with any other degrees. Intraperitoneal injection of bovine TSH or of immunoglobulins derived from a patient with GD in rabbits induced hyperplastic change of thyroid follicular cells, as reflected in PCNA and c-myc immunoreactivity, as well as strong peroxidase and acid phosphatase activity. Immunization with synthesized peptide of thyrotropin receptor also exhibited the same results in the rabbit thyroids. Our results indicate that c-myc expression on follicular cells of GD may reflect a stimulation by autoantibodies mediated through the thyrotropin receptor. Kenji Kashima, Department of Pathology, Oita Medical University, 1-1 Oita-gun, Oita 879-55, Japan

scholarly journals Overexpression of Metallothionein I/II: A New Feature of Thyroid Follicular Cells in Graves' Disease

2012 ◽  
Vol 97 (2) ◽  
pp. 446-454 ◽  
Author(s):  
M. Ruiz-Riol ◽  
M. J. Martínez-Arconada ◽  
N. Alonso ◽  
B. Soldevila ◽  
D. Marchena ◽  
...  
Keyword(s):  
Graves Disease ◽  
Follicular Cells ◽  
Thyroid Follicular Cells ◽  
New Feature

scholarly journals Planning of 131I Therapy for Graves Disease Based on the Radiation Dose to Thyroid Follicular Cells

2008 ◽  
Vol 49 (12) ◽  
pp. 2026-2030 ◽  
Author(s):  
D. Eterovic ◽  
Z. Antunovic ◽  
V. Markovic ◽  
D. Grosev
Keyword(s):  
Radiation Dose ◽  
131I Therapy ◽  
Graves Disease ◽  
Follicular Cells ◽  
Thyroid Follicular Cells

New Thoughts about the Cause and Treatment of the Severe Ocular Manifestations of Graves' Disease

1974 ◽  
Vol 19 (4) ◽  
pp. 165-169 ◽  
Author(s):  
I. R. McDougall ◽  
J. P. Kriss
Keyword(s):  
Corticosteroid Treatment ◽  
Immunosuppressive Drugs ◽  
Definitive Treatment ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
High Dose ◽  
Ocular Manifestations ◽  
Dose Corticosteroid

The ocular manifestations of Graves' disease are probably due to autoimmunity. Thyroglobulin and complexes of thyroglobulin and antithyroglobulin have a predilection to attach to extraocular muscle membranes in vitro. It is suggested that in vivo these molecules are directed, probably via lymphatics, to the orbit where they attach to the muscle cell membranes. B lymphocytes, which have been shown to be capable of combining with both thyroglobulin and complexes, attach on to these molecules. The tissue damage is probably caused by the complexes, the lymphocytes, or both. Treatment of hyperthyroidism in a patient with ophthalmopathy should be cautious and with antithyroid drugs. This will reduce, though not completely eliminate, the possibility of a post-treatment exacerbation. If for some reason definitive treatment of the hyperthyroidism is essential, worsening of the ophthalmopathy may be prevented by prescribing steroids or immunosuppressive drugs at the time of surgical or radioiodine treatment. When progressive eye disease has arisen, orbital radiotherapy is a safe effective alternative to high dose corticosteroid treatment or surgical decompression.

Thyroid growth-stimulating immunoglobulins in goitrous disease: relationship to thyroid-stimulating immunoglobulins

1986 ◽  
Vol 111 (3) ◽  
pp. 321-330 ◽  
Author(s):  
P. P. A. Smyth ◽  
N. M. McMullan ◽  
B. Grubeck-Loebenstein ◽  
D. K. O'Donovan
Keyword(s):  
G6pd Activity ◽  
Graves Disease ◽  
Follicular Cells ◽  
Structural Variations ◽  
Thyroid Stimulating Immunoglobulins ◽  
Cytochemical Bioassay ◽  
Thyroid Follicular Cells ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Receptor Antibodies ◽  
Relative Potencies

Abstract. Thyroid growth stimulating immunoglobulins (TGI) were assayed in IgG concentrates prepared from human plasma using a cytochemical bioassay (CBA) based on the measurement of changes in glucose-6-phosphate dehydrogenase (G6PD) activity in guinea pig thyroid follicular cells. TGI was present in all 8 patients studied who had goitrous Graves' disease, in 9 who had toxic diffuse goitres with asymmetric uptake on scintigram and/or symptomatic ophthalmopathy and in 4:8 who had toxic uninodular goitre with autonomously functioning nodules. TGI were also present in 34:54 (64%) of patients who had non-toxic goitres. In contrast, TGI were undetectable in 4 patients who had Graves' disease without palpable goitre and in all 18 euthyroid non-goitrous volunteers. Maximum increases in G6PD activity occurred at an IgG concentration of 50 μg/ml in all patients who had goitrous Graves' disease and in 5:7 who had diffuse non-toxic goitres. In contrast, IgG concentrates from 20:27 patients with nodular goitres caused maximum increases in G6PD activity at an IgG concentration of 500 μg/ml. A comparison of the prevalence of TGI with that of thyroid stimulating immunoglobulins (TSI), also measured by CBA, in 63 patients showed that although both stimulators were present in 8 patients who had goitrous Graves' disease they were only simultaneously present in 18:43 (42%) who had non-toxic goitres of various aetiologies. Thyrotrophin receptor antibodies (TRAb) were present in 11/44 (25%) of non-toxic goitrous patients but there was no significant correlation with IgG stimulators in such patients. It is concluded that the finding of IgG stimulators in a variety of thyroid disorders suggests common immunological features in their pathogenesis. The presence or absence of such stimulators and their relative potencies may play a part in determining functional or structural variations between common forms of goitre.

scholarly journals The Transcriptomic Response of the Murine Thyroid Gland to Iodide Overload and the Role of the Nrf2 Antioxidant System

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 884 ◽  
Author(s):  
Dionysios V. Chartoumpekis ◽  
Panos G. Ziros ◽  
Ilias Georgakopoulos-Soares ◽  
Adam A. T. Smith ◽  
Ana Claudia Marques ◽  
...  
Keyword(s):  
Transcriptional Response ◽  
Differentially Expressed ◽  
Graves Disease ◽  
Messenger Rnas ◽  
Follicular Cells ◽  
Transcriptomic Response ◽  
Nrf2 Pathway ◽  
Hormone Synthesis ◽  
Excess Iodide

Background: Thyroid follicular cells have physiologically high levels of reactive oxygen species because oxidation of iodide is essential for the iodination of thyroglobulin (Tg) during thyroid hormone synthesis. Thyroid follicles (the functional units of the thyroid) also utilize incompletely understood autoregulatory mechanisms to defend against exposure to excess iodide. To date, no transcriptomic studies have investigated these phenomena in vivo. Nuclear erythroid factor 2 like 2 (Nrf2 or Nfe2l2) is a transcription factor that regulates the expression of numerous antioxidant and other cytoprotective genes. We showed previously that the Nrf2 pathway regulates the antioxidant defense of follicular cells, as well as Tg transcription and Tg iodination. We, thus, hypothesized that Nrf2 might be involved in the transcriptional response to iodide overload. Methods: C57BL6/J wild-type (WT) or Nrf2 knockout (KO) male mice were administered regular water or water supplemented with 0.05% sodium iodide for seven days. RNA from their thyroids was prepared for next-generation RNA sequencing (RNA-Seq). Gene expression changes were assessed and pathway analyses were performed on the sets of differentially expressed genes. Results: Analysis of differentially expressed messenger RNAs (mRNAs) indicated that iodide overload upregulates inflammatory-, immune-, fibrosis- and oxidative stress-related pathways, including the Nrf2 pathway. Nrf2 KO mice showed a more pronounced inflammatory–autoimmune transcriptional response to iodide than WT mice. Compared to previously published datasets, the response patterns observed in WT mice had strong similarities with the patterns typical of Graves’ disease and papillary thyroid carcinoma (PTC). Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) also responded to iodide overload, with the latter targeting mRNAs that participate mainly in inflammation pathways. Conclusions: Iodide overload induces the Nrf2 cytoprotective response and upregulates inflammatory, immune, and fibrosis pathways similar to autoimmune hyperthyroidism (Graves’ disease) and PTC.

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