metallothionein and Graves-Disease

The expression of metallothionein I/II (MT-I/II) was examined in thyroids of Graves' disease (GD) and nodular goiter (NG) patients to determine its role as a potential marker of proliferation and autoimmune inflammation in the thyroid.. MT-I/II and Ki-67 antigen expression was studied using immunohistochemistry in 72 GD and 24 NG patients.. MT-I/II expression was noted in the cytoplasm and nuclei of thyrocytes of GD and NG patients. Cytoplasmic and nuclear MT-I/II expression correlated strongly with GD (r=0.51; p<0.0001) and NG (r=0.50; p=0.0137). Cytoplasmic MT-I/II expression was significantly higher in GD (mean IRS 9.24±2.36) than in NG (mean IRS 7.13±2.51; p=0.0006) and correlated positively with Ki-67 antigen expression (r=0.28; p=0.0165). Nuclear MT-I/II expression was elevated in GD (mean 3.53±0.65) in comparison to NG (mean 2.96±0.86; p=0.028).. MT-I/II may be a potential marker of GD in the thyroid and may be potentially involved in thyrocytes' proliferation.

Topics: Adolescent; Adult; Aged; Cell Nucleus; Female; Goiter, Nodular; Graves Disease; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Metallothionein; Middle Aged; Thyroid Gland; Young Adult

One salient feature of autoimmune thyroid disease is the inappropriate expression of human leukocyte antigen (HLA) class II molecules by thyroid follicular cells. Metallothioneins (MT) are small proteins induced by tissue stress that can contribute to restoring homeostasis of tissue inflammation and have been found to be increased in a transcriptomic analysis of Graves' disease (GD) glands.. To assess the role of MT in the pathogenesis of GD, we analyzed MT-I and -II expression and distribution in GD-affected thyroid glands (n = 14) compared with other thyroid diseases (n = 20) and normal thyroid glands (n = 5). Two-color indirect immunofluorescence and semiquantitative morphometry were applied. The relationship between MT and HLA class II expression was analyzed by their degree of colocalization in GD sections, and in vitro induction kinetics and expression of these molecules on the HT93 thyroid cell line were compared by quantitative RT-PCR and flow cytometry using interferon-γ and zinc as stimuli.. MT were clearly overexpressed in nine of 14 GD glands. MT expression distribution in GD was almost reciprocal to that of HLA class II. In vitro analysis of MT and HLA class II demonstrated that MT is induced more slowly and at a lower level than HLA. Moreover, the main MT inducer, zinc, reduces interferon-γ-induced class II expression.. These findings show that MT and HLA class II play very different roles in the autoimmune process by affecting the thyroid gland, thereby pointing to the possible role of MT as a marker of cell stress and homeostasis restoration in GD.

Topics: Adolescent; Adult; Aged; Cells, Cultured; Cohort Studies; Female; Gene Expression Regulation; Graves Disease; Humans; Male; Metallothionein; Middle Aged; Stress, Physiological; Thyroid Gland; Up-Regulation; Young Adult