Graves' disease is characterized by the increased number of CD4+ T cells and CD8+ T cells. Hashimoto's thyroiditis is characterized by the low number of CD4+ T cells and increased number of CD8+ T cells. CD8+ T cells have cytotoxic properties only in Hashimoto's thyroiditis.
Background: Iodine prophylaxis in Poland started in 1935 and has been interrupted twice: by World War II and in 1980 for economic reasons. Epidemiological surveys carried out after the Chernobyl accident in 1989 as well as in 1992/1993 and in 1994 as a`ThyroMobil' study, revealed increased prevalence of goitre in children and adults. Ninety per cent of Poland was classified as an area of moderate iodine deficiency, and 10%, in the seaside area, as mild iodine deficiency territory. Iodine prophylaxis based on iodisation of household salt was introduced again in 1986 as a voluntary model and in 1997 as a mandatory model with 30^10 mg KIakg salt. Objective: The evaluation of the obligatory model of iodine prophylaxis in schoolchildren from the same schools in 1994 and 1999. Methods: Thyroid volume was determined by ultrasonography. Ioduria in casual morning urine samples was measured using Sandell±Kolthoff 's method, within the framework of the ThyroMobil study. Results: Goitre prevalence decreased from 38.4 to 7% and urinary iodine concentration increased from 60.4 to 96.2 mg/l mean values between 1994 and 1999. In four schools the prevalence of goitre diminished below 5%. In 1999, 70% of children excreted over 60 mg I/l, and 36% over 100 mg I/l, whereas in 1994 the values were 44 and 13% respectively. Conclusion: The present findings indicate that iodine prophylaxis based only on iodised household salt is highly effective.
Implementation of the new model of iodine prophylaxis in Poland in 1997 has led to significant increase in iodine urinary concentration and decrease in goiter prevalence among Polish schoolchildren. In the youngest group of children (6-8 yr olds), prevalence of goiter decreased to 3.2%--i.e. below endemic levels.
Almost all cases of hyperthyroidism in children result from Graves' disease (GD). Recent studies have confirmed a significant role of T regulatory cells (Tregs) in the development of autoimmune diseases. However, the interactions between T cell responses and Treg proliferation in GD are still poorly understood. The aim of this study was to assess the proliferation of Treg cells (Tregs) and CD3+ T lymphocytes isolated from 50 children with GD before and after treatment with the thyreostatic drug methimazole (MMI). The proliferation rates, measured by methyl-3H-thymidyne incorporation, of CD3+ cells and Tregs stimulated with mitogen phorbol 12-myristate 13-acetate (PMA) were compared with those of unstimulated cells. The proliferation rates of both PMA-stimulated and unstimulated CD3+ cells prior to treatment with MMI were significantly higher than after treatment. Simultaneously, the proliferation rates of both PMA-stimulated and unstimulated Tregs were significantly lower before MMI treatment. Moreover, we observed higher cell proliferation rates of unstimulated and PMA-stimulated Tregs before the initiation of MMI therapy and after treatment in patients who had no relapse of hyperthyroidism. There was a positive correlation between the CD3+ cells proliferation rate before MMI treatment and fT3, as well as fT4 concentration in peripheral blood. The proliferation rates of CD3+ T cells before and after MMI treatment positively correlated with the TSI index. Thus, children suffering from Graves' disease presented lower Tregs proliferative potential compared with CD3+ T cells. Cocultures of CD3+ T cells and Tregs showed that Tregs were not capable of efficiently inhibiting the proliferation of CD3+ T cells in GD patients. Conclusions. MMI treatment reduced the proliferative activity of CD3+ T cells in pediatric GD patients and increased the proliferation rate of Tregs. We suggest that Treg cells that are partly dysfunctional in GD disease are probably suppressed by CD3+ T cells and that methimazole exerts some immunomodulatory effects.
Background: The mechanism of autoimmune reaction, a diffuse process consisting of a combination of epithelial cell destruction, lymphoid cellular infiltration, and fibrosis in Hashimoto’s thyroiditis, is not well known. The aim of this study was to analyse the cell subsets in thyroid tissue of patients with Hashimoto’s thyroiditis. Methods: We studied paraffin-embedded thyroid specimens obtained from children with Hashimoto’s thyroiditis and children without an autoimmune thyroid disease. Mononuclear T cells were detected by means of CD3+, CD4+, CD8+ antibodies, B cells by CD79 alpha+ antibodies, and antigen-presenting cells by CD1a+ antibodies, and they were counted in every 1,000 cells. The specimens from each patient were routinely estimated and investigated under the electron microscope. Results: In Hashimoto’s thyroiditis, we observed a statistically significant increase in T suppressor/cytotoxic cells CD8+ (20.54 ± 0.68%) in comparison to the control group (0.65 ± 0.30%), simple goitre (4.01 ± 5.54%) and nodular goitre (8.53 ± 2.37%), and a statistically significant increase in plasma CD79 alpha+ cells (31.65 ± 9.11%) in comparison to the control group (4.11 ± 1.94%), simple goitre (1.83 ± 0.64%) and nodular goitre (5.22 ± 1.63%). Simultaneously, we observed a low number of CD4+ T helper cells in the thyroid gland (0.93 ± 0.99%) in Hashimoto’s thyroiditis (0.19 ± 0.05% in the control group, 1.05 ± 2.71% in simple goitre, 2.03 ± 1.06% in nodular goitre). The ultrastructural investigations showed interactions between T cells, plasmocytes, fibrocytes and thyrocytes leading to apoptosis of thyrocytes. An immunological synapse between T cells, plasmocytes and thyrocytes in the thyroid gland was noticed. Conclusions: In Hashimoto’s thyroiditis, autoantigen presentation in combination with a low number of CD4+ T helper cells and a high number of CD8+ cells and plasmocytes caused the development of a cytotoxic reaction against thyrocytes, leading to apoptosis of the thyrocytes.
Background: Graves’ disease is the archetype for organ-specific autoimmune disorders. It is very important for our understanding of the mechanisms responsible for progression of autoimmunity. The aim of this study was to present interactions of lymphocytes and thyrocytes in the thyroid tissue in Graves’ disease and nonautoimmune thyroid diseases. Methods: The study involved 30 children with Graves’ disease, 30 children with nodular goiter, 30 with simple goiter and 30 healthy children. After thyroidectomy, T cells were detected in the thyroid specimens by CD3, CD4, CD8 antibodies, B cells by CD79α antibodies and the antigen-presenting dendritic cells with CD1a antibodies (DakoCytomation) and were examined in the EM 900 Zeiss Germany Electron Microscope. Results: The most enhanced immune reaction was observed in the thyroid from children with Graves’ disease. The cells of the immune system infiltrated the thyroid follicles and interfollicular compartments; they also formed lymph follicles. Conclusion: The immune reaction in Graves’ disease and migration of lymphocytes T and B between thyrocytes results in the thickening of the basal membrane of the thyroid follicle. No cytotoxic effect of T cytotoxic/suppressor CD8+ cells on thyrocytes was observed in Graves’ disease, while a mild cytotoxic effect was observed in non-autoimmune thyroid disease.
Introduction: The objective of this study was to analyse the effects of the first three years of treatment with recombinant human insulinlike growth factor 1 (rhIGF-1) in patients from the Polish population. Material and methods: Twenty-seven children (22 boys and five girls) aged 2.8 to 16.0 years old were qualified for treatment with rhIGF-1 (mecasermin) in different treatment centres, according to Polish criteria: body height below-3.0 SD and IGF-1 concentration below percentile 2.5 with normal growth hormone (GH) levels. Mecasermin initial dose was 40 μg/kg bw twice a day and was subsequently increased to an average of 100 μg/kg bw twice a day. Body height, height velocity, weight, body mass index (BMI), and adverse events were measured. Results: Mecasermin treatment resulted in a statistically significant increase in body height (1.45 ± 1.06 SD; p < 0.01) and height velocity in comparison with pre-treatment values. The biggest change in height velocity happened during the first year and diminished during subsequent years. Body weight and BMI also increased significantly after treatment (1.16 ± 0.76 SD and 0.86 ± 0.75 SD, respectively; p < 0.01). Eight patients reported adverse events. These were mild and temporary and did not require treatment modification except in two patients. Conclusions: Treatment with rhIGF-1 was effective and safe in Polish patients with primary IGF-1 deficiency. It had a clear beneficial effect on the height of the patients and significantly accelerated the height velocity, particularly in the first year of treatment.
The primary defect of immunoregulation in children with GD is probably dependent on a large number and the activity of T helper cells and on a small number and hypofunction of T suppressor cells. The amount of lymphocytes decreased proportionally to the duration of methimazole treatment. The thyrocytes probably can present antigens.
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