Intrathyroidal cytokine gene expression profiles in autoimmune thyroiditis

1994 ◽  
Vol 141 (2) ◽  
pp. 309-315 ◽  
Author(s):  
R Paschke ◽  
F Schuppert ◽  
M Taton ◽  
T Velu

Abstract Cytokines are thought to mediate the initiation and perpetuation of autoimmune thyroiditis. However, this concept is mainly based on in vitro findings and to date only interleukin (IL)-6 and interferon-γ (IFN-γ) have been detected in Graves' disease in vivo. The cytokine pattern produced by T-helper (Th) cells has important regulatory effects on the nature of the immune response. We therefore determined these cytokine mRNAs in Graves' disease and Hashimoto's thyroiditis. RNA was extracted by cesium chloride gradient centrifugation from the thyroid tissue of 12 patients undergoing thyroid resection for Graves' disease and from two patients being treated for Hashimoto's thyroiditis. Two patients with parathyroid adenomas and one patient with a goiter were used as controls. RNA was also extracted from normal human thyroid epithelial cells in primary culture. The cDNAs were prepared by reverse transcription and amplified for IL-2, -4, -5, -6 and -10 and IFN-γ by polymerase chain reaction. All the cytokine mRNAs were detected in the Hashimoto's thyroid glands in large quantities. Six of the 12 Graves' disease thyroid glands showed, when compared with controls, an increased accumulation of transcripts for: IFN-γ, IL-2, -4 and -10 or IL-2, -4 and IFN-γ or IL-2 and IFN-γ or IFN-γ alone, each in one case or IL-2 alone in two cases. These cytokine profiles were not representative of a Th1 or Th2 phenotype. Increased amounts of cytokine mRNA in thyroid glands from Graves' disease patients were mostly associated with high microsomal antibody titres and/or prominent intrathyroidal lymphocytic infiltration. IL-6 and/or IL-10 mRNAs were detectable in all Graves' disease thyroid glands and in control thyroid tissue. IL-10 mRNA was not detectable in normal human thyroid epithelial cells in primary culture. Graves' disease and Hashimoto's thyroiditis clearly differ with respect to the number of positive intrathyroidal cytokine mRNAs and their levels. The different cytokine patterns in Graves' disease and in Hashimoto's thyroiditis could reflect the clinical spectrum of autoimmune thyroiditis which is characterized by thyroid tissue destruction and/or thyroid autoantibody production. These data suggest that the course of autoimmune thyroiditis is regulated by the interplay of several cytokines. Journal of Endocrinology (1994) 141, 309–315

1991 ◽  
Vol 125 (5) ◽  
pp. 502-509 ◽  
Author(s):  
Hiroyuki Ohashi ◽  
Tadamasa Okugawa ◽  
Mitsuyasu Itoh

Abstract. To investigate the relationships between lymphocyte subsets and thyroid function, peripheral blood lymphocytes were analysed with cell surface antigens of activated (HLA-DR+) T, helper T (CD4+2H4−, CD4+4B4+) and suppressor-inducer T (CD4+2H4+, CD4+4B4−) cells subsets in 56 patients with Graves' disease, 16 patients with Hashimoto's thyroiditis, 7 patients with typical subacute thyroiditis and 2 patients with the thyrotoxic phase of autoimmune thyroiditis. Both patients with Graves' disease and Hashimoto's thyroiditis had increased percentages of HLA-DR+T (Ia+CD3+) cells as well as HLA-DR+ helper-inducer T (Ia+CD4+) cells, which seemed to be independent of treatments. The percentage of HLA-DR+ suppressor-cytotoxic T (Ia+CD8+) cells was increased in euthyroid or hypothyroid patients with Graves' disease following treatment, but was normal in hyperthyroid patients. The percentages of Ia+CD4+ cells and Ia+CD8+ were also increased in patients with thyrotoxic phases of subacute thyroiditis and autoimmune thyroiditis, whereas these abnormal values normalized in the remission phase. These findings suggest that an increase in Ia+CD4+ cells characteristically occurs during immune system activation in patients with hyperthyroid Graves' disease, Hashimoto's thyroiditis and the thyrotoxic phase of subacute thyroiditis, whereas the activated CD8+ cells in Graves' disease are induced by antithyroidal therapy.


2004 ◽  
pp. 587-594 ◽  
Author(s):  
N Koriyama ◽  
M Nakazaki ◽  
H Hashiguchi ◽  
K Aso ◽  
Y Ikeda ◽  
...  

OBJECTIVES: The examination of potential associations between Graves' disease and thyrotropin-producing pituitary adenoma (TSHoma) after treatment using octreotide, and of the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma). DESIGN AND METHODS: A specimen of resected TSHoma tissue from our case was immunohistochemically examined for expression of somatostatin receptor 2A (SSTR2A) and PPAR gamma. Specimens of thyroid tissue from two cases with Hashimoto's thyroiditis were immunohistochemically examined for expression of SSTR2A. RESULTS: Expression of SSTR2A and PPAR gamma was identified in TSHoma cells. SSTR2A was also expressed in lymphocytes that had infiltrated thyroid tissue in Hashimoto's thyroiditis. In previous reports, three of four patients with TSHoma displayed Graves' disease after tumor resection, and TSH is also known to play a major role in regulating immunomodulatory gene expression in thyrocytes. CONCLUSIONS: Both the immunomodulatory effects of octreotide on intrathyroidal lymphocytes and rapid reductions in TSH may contribute to the onset of Graves' disease. Patients with TSHoma-associated autoimmune thyroiditis should undergo careful follow-up for development of Graves' disease after treatment. Both octreotide and the PPAR gamma receptor-activating ligands, thiazolidinediones, may be effective for patients with TSHoma.


1979 ◽  
Vol 91 (1) ◽  
pp. 99-108 ◽  
Author(s):  
Akira Sugenoya ◽  
Jay Silverberg ◽  
Krinos Trokoudes ◽  
Vas V. Row ◽  
Robert Volpé

ABSTRACT The formation of macrophage-lymphocyte rosettes was studied in lymphocyte cultures from patients with Graves' disease, Hashimoto's thyroiditis, other thyroid diseases and control subjects; the cultures were incubated with normal human thyroid and other non-specific antigens. At the end of incubation, the cell pellets were smeared on slides, stained with Wright's stain and the number of rosettes determined under the microscope. The membrane immunofluorescence technique was employed to identify whether the surrounding lymphocytes were T- or B-lymphocytes. In Graves' disease and Hashimoto's thyroiditis, the mean percentages of rosette formation with crude thyroid antigen were 0.98 ± 0.22 % (mean ± sem), and 1.15 ± 0.25 %, respectively. These values were significantly higher than those of control lymphocytes (0.03 ± 0.02 %). Lymphocytes from other thyroid diseases also gave higher values than controls. Kidney antigen, used as a control antigen, gave negative results in Graves' disease and other thyroid diseases, but in Hashimoto's thyroiditis, the mean percentage was of borderline significance. In the direct immunofluorescent staining study using fluorescein-conjugated goat anti-human Ig determinants, including the Fab fraction of anti-human IgG, it appeared that both B- and T-lymphocytes were involved in the rosettes, although B-lymphocytes were more numerous. These results indicate that in patients with Graves' disease and Hashimoto's thyroiditis, a probable immune reaction with thyroid antigen can be demonstrated by macrophage-lymphocyte rosette formation.


1977 ◽  
Vol 84 (4) ◽  
pp. 759-767 ◽  
Author(s):  
Christian von Westarp ◽  
Andrew J. S. Knox ◽  
Vas V. Row ◽  
Robert Volpé

ABSTRACT Antibodies were raised to various sub-cellular fractions of human thyroids, (of Graves' disease, Hashimoto's thyroiditis, and non-toxic goitre). With one exception it was found that antibodies to the Graves' thyroid fractions cross-reacted with both the non-toxic goitre and Hashimoto's thyroiditis fractions. This exception was in the antiserum to the Graves' 105 000 × g pellet (Gr4) which contained an antibody (A-1) that could not be absorbed by either the non-toxic goitre (NTG) or the Hashimoto's (H) thyroid preparations. The antibody-antigen reaction between A-1 and Gr4 could be blocked by the addition of LATS (or TSH) to the antigen, thus suggesting that A-1 might be a LATS-like immunoglobulin. These results suggest that the TSH receptor may be antigenic and that an antibody to this receptor can be produced in vivo. Production of such an antibody to the TSH receptor would permit the development for the first time of a good animal model of Graves' disease.


2006 ◽  
Vol 154 (1) ◽  
pp. 13-20 ◽  
Author(s):  
G Aust ◽  
K Krohn ◽  
N G Morgenthaler ◽  
S Schröder ◽  
A Schütz ◽  
...  

Objective: To report on the rare simultaneous occurrence of Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) in monozygotic twins. Design: We compared the pattern of thyroid tissue-derived cDNAs to gain insight into previous and ongoing immune destruction and reconstruction processes using microarrays. The results were confirmed by immunohistology and real-time PCR. Results: Destruction of thyroid tissue in HT reduced levels of thyrocyte-related cDNAs and cDNAs encoding extracellular matrix components, but increased levels of proteases involved in extracellular matrix degradation compared with GD. Lymphocytic infiltrates forming ectopic follicles replaced the thyroid tissue almost completely in HT. Thus, lymphocyte-related cDNA levels were higher in HT than in GD. The same was true for many chemokines and their receptors, which not only enable migration towards the thyroid but also maintain the lymphocytic infiltrate. HT also showed increased levels of cDNAs encoding molecules related to apoptosis than did GD. Surprisingly, the Th1- and Th2-specific cytokine profiles suggested for HT and GD respectively could not be confirmed. cDNAs encoding factors and receptors involved in angiogenesis were increased in GD compared with HT. Conclusions: Comparison of gene expression reflects the cellular differences between the two types of autoimmune thyroid disease in twins with identical genetic and similar environmental background.


1982 ◽  
Vol 101 (2) ◽  
pp. 199-204
Author(s):  
Angeles A. Garcia ◽  
Anthony N. Hunter ◽  
John A. Wilkins ◽  
Christian von Westarp

Abstract. Two different thyroid membrane preparations (TMP), crude and pure, made from a homogenate of normal human thyroid tissue, were used to test purified serum IgG from 36 patients with Graves' disease, and 10 normal control subjects, in the thyrotrophin-binding-inhibition (TBI) assay. All reagents for the assay were identical, and aliquots of each IgG were tested in both TMP simultaneously, under exactly comparable conditions. Blood was drawn while the patients were hyperthyroid (19), euthyroid (13), or hypothyroid (4); 15 of the patients were untreated and 21 were being treated. The frequency of positive TBI was similar in both TMPs and highest among the 131I-treated patients. Comparison of TBI results in both TMP for each IgG sample revealed wide differences, and 47.1% of the Graves' IgGs were TBI positive in one membrane preparation, while negative in the other. There was no correlation of TBI values between the two TMP, or with clinical status, or the presence of standard thyroid antibodies. The findings indicate that the IgGs of Graves' disease, as now tested in the TBI assay, bind heterogeneous to different fractions of the thyroid membranes.


2000 ◽  
Vol 39 (05) ◽  
pp. 133-138 ◽  
Author(s):  
W. Dembowski ◽  
H.-J. Schroth ◽  
K. Klinger ◽  
Th. Rink

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.


Author(s):  
Nadia Khessairi ◽  
Ibtissem Oueslati ◽  
Ons Rjeb ◽  
Fatma Chaker ◽  
Meriem Yazidi ◽  
...  

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