Critical amino acid variants in HLA-DRB1 allotypes in the development of Graves’ disease and Hashimoto’s thyroiditis in the Japanese population

The effects of amino acid variants encoded by the human leukocyte antigen (HLA) class II on the development of classical type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA) have not been fully elucidated. We retrospectively investigated the HLA-DRB1 and -DQB1 genes of 72 patients with classical T1D and 102 patients with LADA in the Japanese population and compared the frequencies of HLA-DRB1 and -DQB1 alleles between these patients and the Japanese populations previously reported by another institution. We also performed a blind association analysis with all amino acid positions in classical T1D and LADA, and compared the associations of HLA-DRB1 and -DQB1 amino acid positions in classical T1D and LADA. The frequency of DRß-Phe-13 was significantly higher and those of DRß-Arg-13 and DQß-Gly-70 were significantly lower in patients with classical T1D and LADA than in controls. The frequencies of DRß-His-13 and DQß-Glu-70 were significantly higher in classical T1D patients than in controls. The frequency of DRß-Ser-13 was significantly lower and that of DQß-Arg-70 was significantly higher in LADA patients than in controls. HLA-DRß1 position 13 and HLA-DQß1 position 70 could be critical amino acid positions in the development of classical T1D and LADA.

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Abstract #335: Resistance to Thyroid Hormone in Two Siblings Associated With Hashimoto’s Thyroiditis and Graves’ Disease

Endocrine Practice ◽

10.1016/s1530-891x(20)44081-9 ◽

2006 ◽

Vol 12 ◽

pp. 11

Author(s):

Anpalakan Sathasivam ◽

Cheryl R. Rosenfeld

Keyword(s):

Thyroid Hormone ◽

Hashimoto’S Thyroiditis ◽

Hashimoto's Thyroiditis ◽

Graves Disease ◽

Resistance To Thyroid Hormone

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Impact of the serum thyroglobulin concentration on the diagnostics of benign and malignant thyroid diseases

Nuklearmedizin ◽

10.1055/s-0038-1632259 ◽

2000 ◽

Vol 39 (05) ◽

pp. 133-138 ◽

Cited By ~ 4

Author(s):

W. Dembowski ◽

H.-J. Schroth ◽

K. Klinger ◽

Th. Rink

Keyword(s):

Hashimoto’S Thyroiditis ◽

Thyroid Volume ◽

Nodular Goiter ◽

Thyroid Diseases ◽

Hashimoto's Thyroiditis ◽

Graves Disease ◽

Normal Range ◽

Serum Thyroglobulin ◽

Diffuse Goiter ◽

Hyperthyroid Patients

Summary Aim of this study is to evaluate new and controversially discussed indications for determining the thyroglobulin (Tg) level in different thyroid diseases to support routine diagnostics. Methods: The following groups were included: 250 healthy subjects without goiter, 50 persons with diffuse goiter, 161 patients with multinodular goiter devoid of functional disorder (108 of them underwent surgery, in 17 cases carcinomas were detected), 60 hyperthyroid patients with autonomously functioning nodular goiter, 150 patients with Hashimoto’s thyroiditis and 30 hyperthyroid patients with Graves’ disease. Results: The upper limit of the normal range of the Tg level was calculated as 30 ng Tg/ml. The evaluation of the collective with diffuse goiter showed that the figure of the Tg level can be expected in a similar magnitude as the thyroid volume in milliliters. Nodular tissue led to far higher Tg values then presumed when considering the respective thyroid volume, with a rather high variance. A formula for a rough prediction of the Tg levels in nodular goiters is described. In ten out of 17 cases with thyroid carcinoma, the Tg was lower than estimated with thyroid and nodular volumes, but two patients showed a Tg exceeding 1000 ng/ml. The collective with functional autonomy had a significantly higher average Tg level than a matched euthyroid group being under suppressive levothyroxine substitution. However, due to the high variance of the Tg values, the autonomy could not consistently be predicted with the Tg level in individual cases. The patients with Hashimoto’s thyroiditis showed slightly decreased Tg levels. In Graves’ disease, a significantly higher average Tg level was observed compared with a matched group with diffuse goiter, but 47% of all Tg values were still in the normal range (< 30 ng/ml). Conclusion: Elevated Tg levels indicate a high probability of thyroid diseases, such as malignancy, autonomy or Graves’ disease. However, as low Tg concentrations cannot exclude the respective disorder, a routine Tg determination seems not to be justified in benign thyroid diseases.

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A sensitive method for assaying thyroid stimulating immunoglobulins of Graves' disease: use of the guanyl nucleotide-amplified thyroid adenylate cyclase assay

Acta Endocrinologica ◽

10.1530/acta.0.1030345 ◽

1983 ◽

Vol 103 (3) ◽

pp. 345-351 ◽

Cited By ~ 7

Author(s):

E. Macchia ◽

P. Carayon ◽

G. F. Fenzi ◽

S. Lissitzky ◽

A. Pinchera

Keyword(s):

Adenylate Cyclase ◽

Hashimoto’S Thyroiditis ◽

Plasma Membranes ◽

Hashimoto's Thyroiditis ◽

Graves Disease ◽

Tissue Preparation ◽

Thyroid Cells ◽

Significant Stimulation ◽

Adenylate Cyclase Stimulation ◽

Sensitive Method

Abstract. The purpose of this study was to develop and validate a sensitive method for evaluating adenylate cyclase stimulation by thyroid-stimulating antibodies (TSAb), based on the measurement of thyroid membrane adenylate cyclase activity in the presence of a non-hydrolyzable GTP analogue, guanyl-5'-yl imidodiphosphate (Gpp(NH)p). The addition of Gpp(NH)p (10−5 m) produced a 10-fold increase of the sensitivity of the system for both TSH and TSAb. Immunoglobulin G preparations from sera of 30 patients with Graves' disease were tested for the adenylate cyclase stimulation either in the presence or in the absence of Gpp(NH)p: a significant stimulation was observed in 27/30 patients when the GTP analogue was added to the system, while only 20/30 patients were positive in the absence of the nucleotide. The advantage of Gpp(NH)p addition was also evident in a large series which included 57 patients with Graves' disease, 15 with Hashimoto's thyroiditis or primary myxoedema and 22 normal subjects. In fact, 88% of patients with Graves' disease resulted positive, while no significant stimulation was elicited by Hashimoto's thyroiditis, primary myxoedema and by normal immunoglobulins. The sensitivity achieved in our system which employs thyroid plasma membranes was similar to that obtained by other investigators with the use of thyroid slices or thyroid cells in primary culture. Furthermore, methods based on thyroid plasma membranes are supposed to have a better reproducibility, since the same tissue preparation, if appropriately stored, may be used in several different tests.

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Defect of a subpopulation of natural killer immune cells in Graves’ disease and Hashimoto’s thyroiditis: normalizing effect of dehydroepiandrosterone sulfate

Acta Endocrinologica ◽

10.1530/eje.1.01906 ◽

2005 ◽

Vol 152 (5) ◽

pp. 703-712 ◽

Cited By ~ 15

Author(s):

Sebastiano Bruno Solerte ◽

Sara Precerutti ◽

Carmine Gazzaruso ◽

Eleonora Locatelli ◽

Mauro Zamboni ◽

...

Keyword(s):

Nk Cells ◽

Hashimoto’S Thyroiditis ◽

Nk Cell ◽

Secretory Activity ◽

Thyroid Diseases ◽

Hashimoto's Thyroiditis ◽

Graves Disease ◽

Autoimmune Thyroid Diseases ◽

Autoimmune Thyroid ◽

Tnf Α

Background: The study of the natural killer (NK) immune compartment could provide important findings to help in the understanding of some of the pathogenetic mechanisms related to autoimmune thyroid diseases (Graves’ disease (GD) and Hashimoto’s thyroiditis (HT)). Within this context, it was suggested that alterations in NK cell cytotoxicity (NKCC) and NK production of cytokines might occur in subjects with GD and HT, whereas the normalization of NK functions could potentially contribute to the prevention of the onset or the progression of both diseases. Objective: Due to the hypothesis of alterations in NK in autoimmune thyroid diseases, we were interested to evaluate NKCC in GD and HT patients and to modulate NK function and secretory activity with cytokines and dehydroepiandrosterone sulfate (DHEAS) in an attempt to normalize NK cell defect. Design: We studied 13 patients with recent onset Graves’ disease, 11 patients with Hashimoto’s thyroiditis at first diagnosis and 15 age-matched healthy subjects. Methods: NK cells were concentrated at a density of 7.75 × 106 cells/ml by negative immunomagnetic cell separation and validated by FACScan as CD16 + /CD56 + cells. NK cells were incubated with interleukin-2 (IL-2) and interferon-β (IFN-β) and co-incubated with DHEAS at different molar concentrations for measuring NKCC and the secretory pattern of tumor necrosis factor-α (TNF-α) from NK cells. Results: Lower spontaneous, IL-2- and IFN-β-modulated NKCC was demonstrated in GD and HT patients compared with healthy subjects (P < 0.001). A decrease in spontaneous and IL-2-modulated TNF-α release from NK cells was also found in both groups of patients (P < 0.001). The co-incubation of NK cells with IL-2/IFN-β + DHEAS at different molar concentrations (from 10−8 to 10−5 M/ml/NK cells) promptly normalized NKCC and TNF-α secretion in GD and HT patients. Conclusions: A functional defect of a subpopulation of NK immune cells, involving both NKCC and the secretory activity, was demonstrated in newly-diagnosed GD and HT patients. This defect can be reversed by a dose-dependent treatment with DHEAS. The impairment of NK cell activity in autoimmune thyroid diseases could potentially determine a critical expansion of T/B-cell immune compartments leading to the generation of autoantibodies and to the pathogenesis of thyroid autoimmunity.

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