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

• Proteinuria in Hashimoto thyroiditis [4].
• When 90% of the gland is destroyed, the secretion of thyroid hormones (T3/T4) falls below normal needs and pituitary thyrotrophs react by producing over 100 times the normal amount of thyroid-stimulating hormone (TSH) which should normally lead to regrowth of the gland as happens in goitrous Hashimoto thyroiditis [5].
• The putative GD and HT susceptibility genes include both immune modifying genes (e.g., human leukocyte antigen, cytotoxic T lymphocyte antigen-4) and thyroid-specific genes (e.g., TSH receptor, thyroglobulin) [6].
• Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT), and some are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT [6].
• The mechanisms responsible for thyrocyte destruction in Hashimoto's thyroiditis (HT) are poorly understood [7].

Chemical compound and disease context of HT

• Studies in animal models of spontaneous Hashimoto's autoimmune thyroiditis (HT) show that prophylactic treatment with levothyroxine (LT4) can reduce incidence and degree of lymphocytic infiltration in HT [8].
• In this study, we examined by flow cytometry and immunohistochemical techniques, the expression of integrin receptors and their counter-receptors by infiltrating lymphocytes and vascular endothelium in thyroid glands from patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT) [9].
• Leucoagglutinin (LAG) and concanavalin A, but not lipopolysaccharide induced HLA-DR expression on thyrocytes from normal subjects (NC) and patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT) [10].
• METHODS: In the first part of the study, 11 patients with HT and subclinical hypothyroidism (SH) were given Simvastatin (20 mg/day) for 8 weeks [11].
• Hashimoto's thyroiditis (HT) is the second most common thyroid lesion next to endemic goitre diagnosed on FNA in iodine (I2) deficient areas [12].

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

• We examined both thyroid volume and intrathyroidal vascular area by color flow Doppler ultrasonography in patients with Graves' disease (GD), Hashimoto's thyroiditis (HT), and subacute thyroiditis [2].
• In the absence of antigen, i.e., the autologous mixed lymphocyte reaction (AMLR), CD8+ and CD8+CD11b+ T lymphocytes from patients with GD and HT showed significantly lower activation as compared to N [33].
• In a cross-sectional study, 29 children aged between 1 month and 15.3 years (average age 6.8 years) born to mothers with Graves disease or Hashimoto thyroiditis were examined clinically, biochemically, and by sonography of the thyroid gland [34].
• PATIENTS AND METHODS: A quantitative real-time PCR assay was developed to measure the proviral load of HTLV-I in peripheral blood mononuclear cells from 26 HTLV-I-infected patients with HT, eight HTLV-I-infected patients with GD, or 38 asymptomatic HTLV-I carriers [35].
• Thyroid tissues from patients with Hashimoto's thyroiditis (HT) have been xenografted to both severe combined immunodeficiency (SCID) mice and nude mice to study the intrathyroidal lymphocytes which were expected to migrate from the xenografts in the SCID mice [36].

References