Circulating T cell subsets in euthyroid Graves' disease

T cell subpopulations recognized by surfaces markers of different functional meaning have been evaluated in 12 female patients with euthyroid Graves' disease and in 2 patients with ophthalmopathy and Hashimoto's thyroiditis. We have used the following markers: i) receptors for Fc fragments of IgG; ii) antigens recognized by the monoclonal antibodies MLR4, 5/9, BT 2/9 (anti-DR). In the 12 patients with euthyroid Graves' disease a marked decrease of TG cells (which proved to exert suppressor function in several in vitro systems) was observed, as previously reported in hyperthyroid Graves' disease. The 2 Hashimoto's patients with eye changes had normal or high TG. 5/9+ T cells (which contain cells with helper activity in vitro), as well as MLR4+ and BT 2/9+ cells (activated T cells) were normal in the majority of patients, but elevated in the 2 Hashimoto's thyroiditis. The observed abnormality of TG cells in euthyroid Graves' disease might be consistent with the hypothesized autoimmune pathogenesis of endocrine ophthalmopathy.     

Antibodies to nuclear antigens in Graves' disease

A recent publication reported a high prevalence of double-stranded DNA antibodies quantitated by RIA in patients with Graves' disease. We, therefore, measured antibodies to a variety of nuclear antigens in 20 patients with Graves' disease, most of whom where hyperthyroid. Fluorescent antinuclear antibody tests using HEp-2 cells as substrate were positive in serum of 15 of the 20 patients but in only 2 of 20 normal subjects. DNA binding, determined by RIA, was increased in 12 of 18 patients with Graves' disease. However, a more specific indirect immunofluorescence assay for antibodies to double-stranded DNA using Crithidia luciliae was negative in all 20 patients. Furthermore, antibodies to single-stranded DNA, measured by counterimmunoelectrophoresis, and ribonucleoprotein and Sm antigens, measured by double diffusion in agar, were undetectable in all patients tested. These results demonstrate a high frequency of antinuclear antibody in patients with Graves' disease. The presence of antibodies to double-stranded DNA was not confirmed when assayed by the highly specific and sensitive Crithidia luciliae method, suggesting nonantibody DNA binding in the DNA RIA.     

Circulating soluble Fas ligand correlates with disease activity in Graves' hyperthyroidism

Apoptosis of thyrocytes may play an important role in the pathogenesis of autoimmune thyroiditis. Meanwhile, the Fas/Fas ligand (FasL) apoptosis pathway has received much attention in physiological homeostasis and immune regulation in various thyroid diseases, including Graves' hyperthyroidism (GD). FasL is a type II membrane protein of the tumor necrosis factor family, and induces apoptosis when it binds to Fas. Soluble FasL (sFasL) may also exert cytotoxic activity against Fas-expressing cells by producing trimerization of Fas molecule, but soluble Fas (sFas) is an apoptotic inhibitor. To determine the role of circulating sFas/sFasL in modulating disease activity of GD, we examined the circulating levels of sFas/sFasL in GD patients with various levels of anti-thyrotropin-stimulating hormone (TSH) receptor antibodies (TRAb). Serum samples were obtained from 22 consecutive untreated hyperthyroid GD patients with higher TRAb level (63.8% +/- 12.5%, group I) and 22 treated euthyroid GD patients, who were in a state of disease remission, with lower TRAb level (7.9% +/-5.9%, group II). The levels of sFas were significantly higher in group I (1.56 +/- 0.26 ng/mL) than in group II (0.76 +/- 0.26 ng/mL, P <.01). The levels of sFasL were also significantly higher in group I patients (0.153 +/- 0.018 ng/mL) than in group II patients (0.126 +/- 0.012 ng/mL, P <.01). A significant correlation was found between sFasL levels and TRAb activity in all GD patients (r = 0.69, P <.01). Because changes in sFasL levels and TRAb levels occur in parallel, increased serum sFasL in patients with GD may contribute to homeostasis in the thyroid. Serum sFasL may be considered to be a candidate marker for evaluating disease aggression or regression in GD.     

Circulating endothelium-related adhesion molecules in black South African patients with Graves' disease

Elevated serum concentrations of endothelium-associated adhesion molecules occur in Graves’ disease. However, no data exist in African subjects, among whom the incidence is rising. Therefore, 20 black South Africans with Graves’ hyperthyroidism were evaluated and 10 healthy controls were also studied. Quantitative determinations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-Selectin (sE-Selectin) were performed in serum samples by an enzyme-linked immunosorbent assay. Mean levels of sVCAM-1 were significantly increased in the thyrotoxic patients compared to controls, but this did not apply to the other adhesion molecules. The presence of ophthalmopathy in 12 patients did not further increase the mean sVCAM-1 concentration, and the administration of antithyroid medication in 5 patients had no measurable effect. In conclusion, sVCAM-1 appears to be a useful marker of active Graves’ disease in black South Africans although it does not seem to reflect the occurrence of eye involvement in such patients.     

Clinical implications of measurement of serum nuclear matrix protein levels in patients with liver disease

BACKGROUND/AIMS: Serum aminotransferase, a sensitive marker of hepatocellular damage, often poorly correlates with the severity of damage. Serum nuclear matrix protein (NMP), a structural protein released from dead cell nuclei, is investigated as a candidate marker of organ damage in liver disease. METHODOLOGY: Serum NMP and aminotransferase levels of 134 patients with various liver diseases and 26 healthy individuals were examined. RESULTS: Patients with chronic viral hepatitis showed slightly higher NMP levels (17.8 U/mL; 95% CI 15.0-20.5 U/mL) than those of healthy individuals (6.05 U/mL; 95% CI 4.82-7.27 U/mL). Their NMP values had no correlation with aminotransferase levels. NMP levels were similar irrespective of liver disease progression, whereas aminotransferase values decreased in parallel with progression. Patients with autoimmune hepatitis or primary biliary cirrhosis who were under an appropriate treatment as well as individuals with fatty liver showed no elevation of serum NMP levels. Patients with acute viral hepatitis showed very high NMP levels (38.8 U/mL; 95%CI 27.6-50.0 U/mL) that correlated with serum aminotransferase levels in their sera. CONCLUSIONS: In chronic liver diseases, the serum NMP level elevates to various degrees independent from the degree of aminotransferase elevation. Serum NMP, putatively representing the number of dead cells, is a candidate as an indicator of organ damage severity in liver disease.     

Hypothyroid Graves' disease

Graves' disease has recently been shown to exist in a euthyroid form in untreated patients. Sporadic reports of a hypothyroid form are beginning to emerge, thus illustrating the multifaceted nature of this disorder, with thyrotoxicosis at one end of the spectrum and hypothyroidism at the other. Three patients with nonthyrotoxic Graves' disease and concomitant hypothyroidism were seen at Emory University Hospital in one year, and deatailed studies were made to help elucidate the nature of this unusual combination. Results of these studies are reported and briefly discussed. It is suggested that, until more is known about this intriguing aspect of the Graves' disease spectrum, the label "hypothyroid Graves' disease" is justifiable.