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Gene Review

HT  -  Hashimoto thyroiditis

Homo sapiens

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Disease relevance of HT

  • We studied the cytokine profile and the immune responses to thyroid antigens of specific T cell clones (TCC) isolated from patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) [1].
  • There was also a significant correlation between serum VEGF and TSH levels in patients with HT who were hypothyroid and had a goiter [2].
  • The serum VEGF levels in untreated patients with subacute thyroiditis were significantly higher than those in patients with untreated GD or HT [2].
  • The follicles of GD tissue in SCID mice were virtually destroyed with ITL, and their appearance was similar to that in HT [3].
  • SCID-TH from GD and HT patients showed transient hyperthyroxinemia, peaking at 2 weeks; these values were significantly higher [free T4, 6.48 +/- 0.90 and 5.50 +/- 0.77 pmol/L (mean +/- SE), respectively; P < 0.05] than SCID-TH from normal controls (2.5 +/- 0.24) [3].

High impact information on HT


Chemical compound and disease context of HT


Biological context of HT

  • In conclusion, HT likely represents a marker of other autoimmunity, rather than being a direct causative agent in CIU [13].
  • These are HT-1 (on chromosome 13q33) and HT-2 (chromosome 12q22) for Hashimoto's thyroiditis (HT), and GD-1 (chromosome 14q31), GD-2 (chromosome 20q11.2), and GD-3 (chromosome Xq21) for Graves' disease (GD) [14].
  • The TSH values of HT patients at the time of diagnosis were compared to CTLA-4 genotype and HLA-DRB4*0101 positivity [15].
  • 6. These data suggest that these two polymorphic sites at CTLA-4 do not play a major role in the susceptibility of the disease in an Italian population while female gender, age over 50 years, HLA DRB1*04-DQB1*0301 haplotype increase the risk of developing HT [16].
  • Our data show a generalized defect in self-tolerance by HT T cells which may have been revealed by preincubation of antigen with restricted numbers of APC and subsequent culture in SFM [17].

Anatomical context of HT

  • Some sera from patients with CIU and HT caused degranulation of normal basophils in the absence of anti-FceRI [13].
  • In this study, we investigated the inhibitory effect of combined expression of human complement regulators and HT on human serum-mediated cytolysis in porcine embryonic fibroblasts [18].
  • Rare detection of phenotypically immature lymphocytes in Hashimoto thyroiditis and rheumatoid arthritis [19].
  • After 1 year of therapy with LT4, TPO-Abs and B lymphocytes decreased significantly only in the treated group of euthyroid patients with HT (p < 0.05) [8].
  • The ratio of HT T helper/inducer cells to T suppressor/cytotoxic cells was elevated at the inception of culture, and further increased during the 9 day culture period [17].

Associations of HT with chemical compounds

  • Inclusion of Tg in serum from HT patients promoted B cell capture of IgG and C3 fragments [20].
  • METHODS: Twenty-four consecutive patients (aged 29-58) with verified HT under levothyroxine therapy were included in the present study [21].
  • In 64 patients with HT, the distribution was similar but not significant (81% homozygous for cytosine and 16% heterozygous) [22].
  • Any difference in triiodothyronine (T3) levels between analysed groups was not detected, while the concentration of thyroxine (T4) was lower in HT than in AFN and significantly decreased after the excision of thyroid gland [23].
  • The asparagine-rich HT protein, originally identified from the style of Nicotiana alata, is the other stylar factor involved in self-incompatibility reaction [24].

Physical interactions of HT

  • TSH inhibited the IFN-gamma enhancement of binding of PBL-T from 4 normals and one HT patient to both allogeneic (n = 5) and autologous (n = 4) THY monolayers [25].

Regulatory relationships of HT

  • Analysis of T-cell receptor genes in T cells derived from the thyroid glands of a patient with Hashimoto's (HT ) autoimmune thyroiditis has shown that the T-cell response in this autoimmune disease is multiclonal [26]
  • T lymphocytes [26] present in thyroid infiltrates of 6 patients with Hashimoto's thyroiditis (HT) and of 4 patients with Graves' disease (GD) were analyzed at clonal level and their profiles of mitogen-induced lymphokine secretion were characterized [27].
  • Furthermore, the binding of Tg to B cells in preparations of normal blood cells was higher in HT serum than in serum from controls and correlated positively with the serum anti-Tg activity, as did the B and CD4+ T cell proliferation [20].
  • In conclusion (1) AMLR reactivity of CD4+ cells from GD and HT was impaired, (2) however, CD4+ cells from both GD and HT were significantly more induced by TPO compared to N, and (3) this induction depends, in part, on the in vivo thyroid status [28].
  • MT3 stimulated proliferation of PBMC when cultured for 2 to 3 days in patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) and in normal controls (NC) [29].
  • The increased positive expressions of CD 83 which is known as a marker of mature and activated DCs in HT (22.58+/-13.96 vs 5.19+/-8.08) and GD (29.92 +/-14.43 vs 5.19+/-8.08) were also found respectively (p<0.001) [30].

Other interactions of HT

  • It is conceivable that in HT, expression of B7.1 on follicular cells, together with MHC class II antigens and ICAM1, could provide a local costimulatory signal for T-lymphocyte differentiation toward the type 1 cytokine secretion pattern and maintenance of the autoimmune process [31].
  • In the present study, we analyzed the possible expression of B7 molecules on surgically removed thyroid tissue of patients with autoimmune [Hashimoto's thyroiditis (HT) or Graves' disease (GD)] or nonautoimmune [nontoxic goiter (NTG) or papillary cancer (PC)] thyroid diseases [31].
  • Paraffin-embedded tissues from 19 HT patients and from 20 RA patients were subjected to immunohistochemistry using TdT-specific antibodies [19].
  • Total PBMC as well as selected PBMC from GD and HT responded to both TPO and Tg, but normal PBMC did not [32].
  • We have examined the distribution of the HLA DRB4*0101 allele and a CTLA-4 exon 1 A/G polymorphism in Japanese HT patients and controls and investigated possible interactions of these genes with thyroid function [15].

Analytical, diagnostic and therapeutic context of HT


  1. Thyrotropin-receptor and thyroid peroxidase-specific T cell clones and their cytokine profile in autoimmune thyroid disease. Fisfalen, M.E., Palmer, E.M., Van Seventer, G.A., Soltani, K., Sawai, Y., Kaplan, E., Hidaka, Y., Ober, C., DeGroot, L.J. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  2. Increased serum vascular endothelial growth factor levels and intrathyroidal vascular area in patients with Graves' disease and Hashimoto's thyroiditis. Iitaka, M., Miura, S., Yamanaka, K., Kawasaki, S., Kitahama, S., Kawakami, Y., Kakinuma, S., Oosuga, I., Wada, S., Katayama, S. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  3. Studies of thyroid xenografts from Graves' disease in severe combined immunodeficient mice. Morita, T., Yoshikawa, N., Akasu, F., Resetkova, E., Arreaza, G., Miller, N., Jamieson, C., Volpé, R. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  4. Proteinuria in Hashimoto thyroiditis. Churchill, D.N., Farid, N. N. Engl. J. Med. (1981) [Pubmed]
  5. Thyroid growth-blocking antibodies in primary myxoedema. Drexhage, H.A., Bottazzo, G.F., Bitensky, L., Chayen, J., Doniach, D. Nature (1981) [Pubmed]
  6. Searching for the autoimmune thyroid disease susceptibility genes: from gene mapping to gene function. Tomer, Y., Davies, T.F. Endocr. Rev. (2003) [Pubmed]
  7. Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto's thyroiditis. Giordano, C., Stassi, G., De Maria, R., Todaro, M., Richiusa, P., Papoff, G., Ruberti, G., Bagnasco, M., Testi, R., Galluzzo, A. Science (1997) [Pubmed]
  8. One-year prophylactic treatment of euthyroid Hashimoto's thyroiditis patients with levothyroxine: is there a benefit? Padberg, S., Heller, K., Usadel, K.H., Schumm-Draeger, P.M. Thyroid (2001) [Pubmed]
  9. Adhesion molecules from the LFA-1/ICAM-1,3 and VLA-4/VCAM-1 pathways on T lymphocytes and vascular endothelium in Graves' and Hashimoto's thyroid glands. Marazuela, M., Postigo, A.A., Acevedo, A., Díaz-González, F., Sanchez-Madrid, F., de Landázuri, M.O. Eur. J. Immunol. (1994) [Pubmed]
  10. Thyrocyte HLA-DR expression and interferon-gamma production in autoimmune thyroid disease. Iwatani, Y., Gerstein, H.C., Iitaka, M., Row, V.V., Volpé, R. J. Clin. Endocrinol. Metab. (1986) [Pubmed]
  11. In vivo and in vitro effects of statins on lymphocytes in patients with Hashimoto's thyroiditis. Gullu, S., Emral, R., Bastemir, M., Parkes, A.B., Lazarus, J.H. Eur. J. Endocrinol. (2005) [Pubmed]
  12. Aspiration cytology of Hashimoto's thyroiditis in an endemic area. Kumar, N., Ray, C., Jain, S. Cytopathology (2002) [Pubmed]
  13. Evaluation of chronic urticaria in patients with Hashimoto thyroiditis. Kandeel, A.A., Zeid, M., Helm, T., Lillie, M.A., Donahue, E., Ambrus, J.L. J. Clin. Immunol. (2001) [Pubmed]
  14. Immunoregulatory and susceptibility genes in thyroid and polyglandular autoimmunity. Dittmar, M., Kahaly, G.J. Thyroid (2005) [Pubmed]
  15. Interactions of HLA-DRB4 and CTLA-4 genes influence thyroid function in Hashimoto's thyroiditis in Japanese population. Terauchi, M., Yanagawa, T., Ishikawa, N., Ito, K., Fukazawa, T., Maruyama, H., Saruta, T. J. Endocrinol. Invest. (2003) [Pubmed]
  16. Association of DRB1*04-DQB1*0301 haplotype and lack of association of two polymorphic sites at CTLA-4 gene with Hashimoto's thyroiditis in an Italian population. Petrone, A., Giorgi, G., Mesturino, C.A., Capizzi, M., Cascino, I., Nistico, L., Osborn, J., Di Mario, U., Buzzetti, R. Thyroid (2001) [Pubmed]
  17. Induction of in vitro autoimmune responses by mononuclear blood cells in Hashimoto's thyroiditis. Stern, S.A., Dau, P.C. Clin. Exp. Immunol. (1987) [Pubmed]
  18. Effects of combined expression of human complement regulatory proteins and H-transferase on the inhibition of complement-mediated cytolysis in porcine embryonic fibroblasts. Lee, J.H., Lee, H.J., Nahm, K.M., Jeon, H.Y., Hwang, W.S., Paik, N.W., Rho, H.M. Transplant. Proc. (2006) [Pubmed]
  19. Rare detection of phenotypically immature lymphocytes in Hashimoto thyroiditis and rheumatoid arthritis. Sening, W., Lisner, R., Niedobitek, G. J. Autoimmun. (2004) [Pubmed]
  20. Autoantibodies in autoimmune thyroid disease promote immune complex formation with self antigens and increase B cell and CD4+ T cell proliferation in response to self antigens. Nielsen, C.H., Hegedüs, L., Leslie, R.G. Eur. J. Immunol. (2004) [Pubmed]
  21. Relation of anti-TPO autoantibody titre and T-lymphocyte cytokine production patterns in Hashimoto's thyroiditis. Karanikas, G., Schuetz, M., Wahl, K., Paul, M., Kontur, S., Pietschmann, P., Kletter, K., Dudczak, R., Willheim, M. Clin. Endocrinol. (Oxf) (2005) [Pubmed]
  22. CTLA-4 promoter variants in patients with Graves' disease and Hashimoto's thyroiditis. Braun, J., Donner, H., Siegmund, T., Walfish, P.G., Usadel, K.H., Badenhoop, K. Tissue Antigens (1998) [Pubmed]
  23. Thyrotropin receptors, thyroid hormones and thyroglobulin in patients with Hashimoto's thyroiditis. Djurica, S., Zakula, Z., Isenović, E., Ratković, M., Ribarac-Stepić, N. Endocrinol. Exp. (1990) [Pubmed]
  24. Cultivated tomato has defects in both S-RNase and HT genes required for stylar function of self-incompatibility. Kondo, K., Yamamoto, M., Matton, D.P., Sato, T., Hirai, M., Norioka, S., Hattori, T., Kowyama, Y. Plant J. (2002) [Pubmed]
  25. Binding of peripheral blood and thyroidal T lymphocytes to thyroid cell monolayers: possible role of homing-like receptors in the pathogenesis of thyroid autoimmunity. Fukazawa, H., Hiromatsu, Y., Bernard, N., Salvi, M., Wall, J.R. Autoimmunity (1991) [Pubmed]
  26. Analysis of T-cell receptor usage in activated T-cell clones from Hashimoto&apos;s thyroiditis and Graves&apos; disease. Lipoldova, M., Londei, M., Grubeck-Loebenstein, B., Feldmann, M., Owen, M.J. J. Autoimmun. (1989) [Pubmed]
  27. High potential to tumor necrosis factor alpha (TNF-alpha) production of thyroid infiltrating T lymphocytes in Hashimoto's thyroiditis: a peculiar feature of destructive thyroid autoimmunity. Del Prete, G.F., Tiri, A., De Carli, M., Mariotti, S., Pinchera, A., Chretien, I., Romagnani, S., Ricci, M. Autoimmunity (1989) [Pubmed]
  28. Studies of CD4+ (helper/inducer) T lymphocytes in autoimmune thyroid disease: demonstration of specific induction in response to thyroid peroxidase (TPO) in vitro and its relationship with thyroid status in vivo. Akasu, F., Kasuga, Y., Matsubayashi, S., Carayon, P., Volpé, R. Thyroid (1991) [Pubmed]
  29. Effects of monoclonal antibody against CD45RB on peripheral blood mononuclear cell proliferation and on HLA-DR and adhesion molecule expression on thyrocytes of patients with autoimmune thyroid disease. Nishikawa, M., Mukuta, T., Arreaza, G., Resetkova, E., Poppema, S., Tamai, H., Volpé, R., Lazarovits, A.I. Thyroid (1995) [Pubmed]
  30. The expression and distribution of S-100 protein and CD 83 in thyroid tissues of autoimmune thyroid diseases. Xu, W., Chen, S., Huang, J., Zheng, Z., Chen, L., Zhang, W. Cell. Mol. Immunol. (2004) [Pubmed]
  31. B7.1 costimulatory molecule is expressed on thyroid follicular cells in Hashimoto's thyroiditis, but not in Graves' disease. Battifora, M., Pesce, G., Paolieri, F., Fiorino, N., Giordano, C., Riccio, A.M., Torre, G., Olive, D., Bagnasco, M. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  32. Sensitization of T lymphocytes to thyroglobulin and thyroperoxidase in autoimmune thyroid diseases. Akasu, F., Morita, T., Resetkova, E., Yoshikawa, N., Carayon, P., Volpé, R. Autoimmunity (1993) [Pubmed]
  33. Reduced activation of suppressor T lymphocytes by specific antigens in autoimmune thyroid disease. Yoshikawa, N., Morita, T., Resetkova, E., Arreanza, G., Carayon, P., Volpé, R. J. Endocrinol. Invest. (1993) [Pubmed]
  34. Thyroid antibodies in children of mothers with auto-immune thyroid disease. Heithorn, R., Hauffa, B.P., Reinwein, D. Eur. J. Pediatr. (1999) [Pubmed]
  35. Human T cell leukemia virus type I-infected patients with Hashimoto's thyroiditis and Graves' disease. Matsuda, T., Tomita, M., Uchihara, J.N., Okudaira, T., Ohshiro, K., Tomoyose, T., Ikema, T., Masuda, M., Saito, M., Osame, M., Takasu, N., Ohta, T., Mori, N. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  36. Reconstitution of severe combined immunodeficient mice with intrathyroidal lymphocytes of thyroid xenografts from patients with Hashimoto's thyroiditis. Akasu, F., Morita, T., Resetkova, E., Miller, N., Akasu, R., Jamieson, C., Volpé, R. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
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