Anti-thyroid antibodies and hypothyroidism in systemic sclerosis.
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Antibodies↗
Biomedical subjects
C Balázs
Publications and source records attributed to C Balázs.
Inhibition of metabolic activity of polymorphonuclear granulocytes by thyroid stimulating antibodies.
Both thyrocytes and polymorphonuclear granulocytes (PMNs) are known to have on their surface thyrotropin receptor (TSH-R). Anti-TSH-R antibodies having stimulating and blocking effects on thyroid function have been detected in sera of Graves' patients. Thyroid stimulating anti-TSH-R antibodies (TSAb) are involved in the pathomechanism of thyrotoxicosis. The basic question is in this study whether TSAb exerts effects on metabolic activity of PMNs. Immunoglobulin G (IgGs) of 32 patients with thyrotoxicosis had significant inhibitory effect (p less than 0.001) on chemiluminescence of healthy PMNs compared to controls. An inverse correlation was observed between inhibitory effect of IgGs on function of PMNs and TT4 (r = -0.61) in contrast to anti-TSH-receptors antibodies (r = 0.09). TSAbs of eight hyperthyroid patients were measured by determination of cyclic AMP in suspension and slices of porcine thyroid gland. Function of human PMNs separated from healthy donors was determined by luminol-amplified chemiluminescence. Photon-emission of PMNs induced by adherence was significantly lower than that of controls. None of patients' IgGs contained anti-PMNs antibodies or other toxic compounds. It was found an inverse correlation between chemiluminescence of PMNs and capability of TSAb to increase intracellular cAMP in thyroid slices and the thyroid hormone levels of patients with thyrotoxicosis (p = 0.0005). In conclusion, TSH-R on PMNs did not belong to "mute" receptors and metabolic changes in PMNs induced by TSAb might have pathogenetic as well as methodological implications.
Adult↗
TSH binding site structures in human eye muscle fractions identified by using covalent-crosslinking.
125I-labelled human TSH was crosslinked to the human thyroid and extraocular eye muscle membrane and cytosol fractions (which were obtained by centrifugation). Studying crosslinking of 125I-labelled TSH to the thyroid fractions, TSH binding sites' structures were demonstrated on the eye muscle membranes and in the cytosol fractions. The binding of 125I-labelled TSH was inhibited by the addition of 120 mIU/mL of unlabelled TSH (and not with 12 mIU/mL) which confirmed the presence of TSH binding sites structures (MW about 66,000 Da) on the eye muscle membrane and in its cytosol. Adding purified IgG fractions from the sera from controls and Graves' disease (with high titer of antibodies against TSH receptor) to the thyroid and eye muscle membranes and cytosol fractions, the binding of 125I-labelled human TSH was inhibited by molecular weight of about 66,000 Da in the cytosol fractions. The affinity constant of the binding sites in the human eye muscle cytosol and the number of TSH receptors were found to be 146 x 10(9) M-1 and 9.8 x 10(10) molecules/mg/mL by Scatchard analysis, respectively.
Cross-Linking Reagents↗
Evaluation of thyroid function and anti-thyroid autoantibodies in systemic sclerosis.
Parameters of thyroid metabolism, and the presence of anti-thyroid antibodies were investigated in 43 patients with systemic sclerosis. Anti-thyroid antibodies were detected in 14 cases. Elevated levels of anti-thyroglobulin antibodies were determined in 4 cases, anti-thyroid peroxidase (TPO) antibodies in 11, and anti-microsomal antibodies in 5. The detection of anti-TPO antibodies gave the most remarkable information about the presence of autoimmune thyroiditis. The patients with anti-TPO and/or reduced T3 concentration tended to have secondary Sjögren's syndrome. Our results provide further evidence that anti-thyroid antibodies might be responsible for the remarkable appearance of autoimmune thyroiditis in systemic sclerosis.
Adult↗
The relationship between anti-human eye muscle antibodies and thyroid function, anti-TSH receptor antibodies and eye symptoms in Graves' ophthalmopathy.
Circulating IgG, IgA, and IgM antibodies to human eye muscle cytosol antigens were studied in 60 patients with Graves' ophthalmopathy using the indirect ELISA method. There was a significant difference in the levels of both IgG and IgA antibodies between the patients with Graves' ophthalmopathy and a control group (p < 0.001). IgA antibodies to eye muscle cytosol antigens were raised in 20 out of 29 patients with proptosis (class 3 ophthalmopathy), in comparison with 31 patients out of the total group of 60 with Graves' ophthalmopathy (p < 0.02). Anti-TSH receptor antibodies (TRAK) were not present in over half of the 31 patients with raised IgA antibodies to eye muscle antigens. However, a significant difference was found between the levels of IgG and IgA antibodies in the TRAK-negative patients (p < 0.05). These findings suggests that both IgG and IgA antibodies to eye muscle antigens might be important in the development of ophthalmopathy.
Adult↗
Effect of ecogramostim on HLA class II antigen expression on thyrocytes.
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Cells, Cultured↗
[The role of antibodies in Graves' ophthalmopathy].
The aim of this study was to investigate the possible pathogenetic role of autoantibodies to eye muscle membrane fractions in 75 patients with Graves' disease (50 patients with infiltrative ophthalmopathy). Autoantibodies directed to four fractions of human eye muscle--as well as thyroid membranes prepared by ultracentrifugation were detected by ELISA and Western blotting techniques. None of autoantibodies to various fractions of eye muscle membrane proved to be specific for Graves' ophthalmopathy, however, the presence of these antibodies and activity of eye symptoms were in correlation. Polyclonal autoantibodies to common epitopes on both thyroid and eye muscle membrane antigens (approximately 60 kD) were revealed that might be involved into pathogenesis of Graves' ophthalmopathy.
Adult↗
Comparative study on IgG and IgA antibodies against human thyroid and eye-muscle antigens in Graves' ophthalmopathy.
Circulating IgG and IgA anti-thyroid and anti-eye muscle antibodies were investigated in 87 patients with Graves' disease (60 cases with ophthalmopathy). The ELISA method was used. Both IgG and IgA antibodies were demonstrated against human thyroid and eye-muscle membrane or cytosol antigens. Anti-eye-muscle antibodies of the IgA type were observed more frequently than those of the IgG type (25 cases vs. 18 were demonstrated with membrane antigens and 37 cases vs. 23 with cytosol antigens). The respective distributions for thyroid antigens the cytosol fraction were 55 cases vs. 13 and 18 cases vs. 36. A significant difference was observed in the anti-thyroid IgG levels and the anti-eye-muscle membrane or cytosol levels between the patients with Graves' disease and those in control group (P less than 0.001). The difference in the IgA antibody to thyroid and eye-muscle antigens was significant between the patients with and without ophthalmopathy (P less than 0.002). The strong correlation between the levels of IgA antibodies to thyroid and those to the eye-muscle cytosol fractions might be connected with the theory of the common aetiology of the thyroid and eye diseases in Graves' ophthalmopathy (P less than 0.001). Circulating IgA anti-human thyroid and eye-muscle antibodies seemed to have a diagnostic relevance in the development of ophthalmopathy in Graves' ophthalmopathy.
Adult↗
Soluble interleukin-2 receptor in sera of patients with Graves' disease.
Recently, in vitro production of interleukin-2 receptor induced by mitogens have been shown to be impaired in autoimmune disorders including organo-specific autoimmune diseases. The aim of this study was to investigate serum levels of soluble interleukin-2 receptor in 20 untreated patients with Graves' disease and to follow up their changes in relation to clinical picture and TSH-receptor-, anti-thyroglobulin-, anti-microsomal as well as anti-eye muscle antibodies. Soluble interleukin-2 receptor level was significantly increased in newly-diagnosed Graves' patients compared to controls (667 +/- 270 vs. 205 +/- 45 U/ml) (P less than 0.001). Among the patients sera those with active infiltrative ophthalmopathy had higher soluble interleukin-2 receptor levels than those without eye symptoms (810 +/- 313 vs. 525 +/- 180 U/ml). Soluble interleukin-2 receptor level was normalized in Methimazole-treatment-induced remission in the majority of patients except those with ophthalopathy. In five patients the soluble interleukin-2 receptor levels were studied after interruption of thyrostatic therapy; an increase was observed in three patients; thereafter hyperthyrosis relapsed in two cases. Furthermore, a correlation was found between soluble interleukin-2 receptor levels and TSH-receptor antibodies, however, the association with other immune parameters examined was not significant. In conclusion, an enhanced level of soluble interleukin-2 receptor was detected in patients with untreated Graves' disease. This finding might play a significant role in regulation of impaired cell-mediated immune mechanism and has a prognostic value for relapse of autoreactive processes.
Adult↗
Cellular and humoral autoimmune responses against human eye muscle membrane antigen in Graves' disease.
75 patients with Graves' disease (54 with ophthalmopathy) were investigated using the tests of leucocyte adherence inhibition and immune adsorption with 125I-labelled Staphylococcus Protein A, against human eye muscle "crude" membrane antigen. The results of positive leucocyte adherence inhibition (10 out of 26 vs. 1 out of 28, P less than 0.05) and anti-human eye muscle membrane antibody index (mean +/- S.D.) (1.89 +/- 1.20 vs. 0.84 +/- 0.38, P less than 0.001) showed a correlation with the patients with clinically active eye disease and the HLA-B8 antigen in Graves' ophthalmopathy (P less than 0.01). Positive leucocyte adherence inhibition was observed in 9 out of 21 cases of Graves' disease without ophthalmopathy, but its prognostic relevance has to be confirmed in the development of ophthalmopathy.
Antibody Formation↗
Effect of lithium on chemiluminescence of polymorphonuclear granulocytes and mononuclear cells of peripheral blood.
Influence of lithium on luminol amplified chemiluminescence activity of leucocytes of human peripheral blood was studied by a continuously recorded system. Lithium had a biphasic effect on mitogen-induced early activation of mononuclear cells, i.e. at concentration of 1.0 mM an increase, at higher concentrations a significant inhibition in photon emission was observed. Activating the mononuclear cells by opsonized Zymosan in the presence of lithium a dose-dependent decrease of chemiluminescence was registered. The respiratory burst of polymorphonuclear granulocytes induced by either mitogen or opsonized Zymosan was significantly inhibited at 2.0 and 5.0 mM of lithium, respectively. Chemiluminescence activity of peroxidase-dependent and independent cell-free system was not influenced by lithium. It was concluded that lithium by accumulating into target organs might have an immunosuppressive and antiphlogistic effect by mean of inhibition of antigen-presenting cells and polymorphonuclear granulocytes.
Granulocytes↗
Time-dependent effect of cyclosporin-A on the TSH-receptor antibody synthesis in patients with Graves' disease.
Two patients with hyperthyroidism and Graves' ophthalmopathy were treated with cyclosporin A (CyA), in addition to methimazole, after failure of steroid therapy. Eye disease showed favorable responses and TSH receptor antibody concentration showed precipitous decline in concentrations compared to a gradual linear decline in antibody concentrations observed in 10 patients not treated with CyA. These results prompted us to investigate the in vitro influence of CyA on the synthesis of TSH receptor antibody by a patient's lymphocytes (with highest antibody concentration) in response to thyroid membrane antigen. CyA caused a dose-dependent reduction of TSH receptor antibody synthesis compared to control cultures. The effect of CyA was more marked when added to lymphocyte culture at the same time rather than 24 h after addition of antigen, consistent with CyA's interference of early T cell triggering by antigen. This study emphasizes the importance of helper T cells in synthesis of TSH-receptor antibody by cells and suggests that the drug may be therapeutically beneficial in severe Graves' ophthalmopathy and/or Graves' hyperthyroidism resistant to conventional treatment.
Adult↗
[Epidemiologic study of immunopathological diseases in a population sample from Hajdú-Bihar County].
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Arthritis, Rheumatoid↗
Atropine is an inhibitor of the chemiluminescence induced by platelet-activating factor in human neutrophils.
Chemiluminescence provoked by platelet-activating factor can be dose-dependently inhibited by atropine. This effect of atropine is rather due to its ion channel blocking capability (at the higher doses than 10(-5) M) than to its action on the acethylcholine receptors. The differences in the roles of platelet-activating factor and acethylcholine in the activation of phagocytes are discussed.
Atropine↗
Identification of lymphocyte subsets in peripheral blood and thyroid gland in Graves' disease by alpha-naphthyl-acetate-esterase reaction.
T lymphocyte subsets were prospectively examined in the peripheral blood and thyroid aspirates of 10 patients with hyperthyroid Graves' disease before and after treatment with methimazole and attainment of euthyroidism. T lymphocyte subsets were identified with monoclonal antibodies and pattern of alpha-naphthyl-acetate esterase (ANAE) staining pattern in the case of peripheral blood and ANAE staining pattern with thyroid aspirate smears. Before treatment, OKT8+ lymphocytes were significantly decreased (18.4% +/- 4.8) (S. D.) in the patients compared to control (28.8 +/- 6.7%, p less than 0.05), the OKT4/OKT8 ratio was increased (2.92 vs 2.11). Percent OKT8+ lymphocytes were not different from the controls when the ten patients had been rendered euthyroid. ANAE mononuclear cells with a diffuse pattern (presumed suppressor cells) were 4.2% +/- 1.8 before treatment and 8.3 +/- 2.4 (p less than 0.05) after treatment and 11.5% +/- 2.2 in controls. ANAE mononuclear cells with diffuse pattern represented 4.2% +/- 1.8 of the mononuclear cells infiltrating the thyroid gland of untreated patients and rose to 8.3% +/- 2.4 after the patients had become euthyroid. ANAE negative cells (B cells and some T cells) were increased in the thyroid of untreated patients. It is concluded that mononuclear cells with presumed suppressor T cell phenotype are decreased in the blood and thyroid glands of patients with active Graves' disease and that this defect is corrected when euthyroidism has been established.
Adult↗
The genetics of Graves' disease: HLA and disease susceptibility.
To relate genetic variation in Graves' disease (GD) susceptibility to polymorphism at MHC loci, clinical and family studies were undertaken in eastern Hungary. Among 1980 relatives of 534 index patients, 2.9% of siblings, 2.7% of offspring, and 3.0% of parents had GD. HLA haplotype combinations in affected sibling pairs were determined in the present data and combined with data in the literature (12 sibling pairs from Farid 1981, 12 from Chan et al. 1980, and 15 from Sasazuki et al. 1983); 43, 23, and 1 affected sibling pairs shared, respectively, 2, 1, and 0 HLA haplotypes. This distribution is inconsistent with simple dominant inheritance, but is consistent with simple recessive inheritance of HLA-related susceptibility over a range of gene frequencies (0.2-0.4). A frequency of 0.3 gives the best fit and is consistent with penetrance of 7.1% for the recessive susceptibility genotype; the data, however, can accommodate penetrance values up to 16%. The distribution of HLA haplotypes in 33 families related disease susceptibility more strongly to DR than to other loci. The distribution of HLA-B8 genotypes in 256 patients was in close agreement with Hardy-Weinberg equilibrium proportions, also favoring recessive inheritance of MHC-related susceptibility. The probability that an individual will be affected with GD can be predicted, based on sex, HLA genotype, and family history. For example, 14.9% of DR3-positive women with an affected first degree relative are likely to be affected. These predictions can be tested as family data accumulate.
Adolescent↗
Experimental glomerular lesions induced by chronic immune complex formation. I. Formation and elimination of the immune complex (relationship between the immune status and the glomerular changes).
Chronic immune complex formation was induced in rabbits by daily administration of 12.5 g bovine serum. In good antibody producer animals immediate immune complex production and elimination from the circulation were demonstrable. This was followed within a few minutes by the appearance of free 125I in fairly large amounts in blood, as a sign of immediate phagocytosis and disintegration of the 125I-labelled immune complexes. Phagocytic activity decreased in the host animal during chronic heteroprotein administration in every case. The earliest glomerular changes were those of exudative glomerulonephritis, the extent of which depended on the antibody productivity of the animal. Persistent immunocomplexaemia induced by administration of the antigen over 60 and 100 days, respectively, resulted in mesangioproliferative glomerulonephritis in 7, in membranoproliferative glomerulonephritis in 3, and in membraneous glomerulonephritis in 1 out of 11 laboratory animals.
Animals↗
Experimental glomerular lesions induced by chronic immune complex formation. II. Pathomorphological analysis.
Eleven rabbits were given bovine serum albumin i.v., in daily doses of 25 mg. Renal biopsy was performed on the 30th, 60th and 100th day of treatment and the specimens were subjected to light-, electron-microscopic and immunofluorescent studies, so as to follow up the dynamics of the glomerular process. Proteinuria and the serum creatinine and BUN levels were also measured. By the 100th day of treatment mesangioproliferative glomerulopathy had developed in 7, membranoproliferative glomerulopathy in 3 cases and membraneous glomerulopathy in 1 case. On the 30th day of treatment exudative glomerulopathy was demonstrable in the majority of the cases (in 9 animals). It is suggested that the earliest stage of the various glomerulopathies, regardless of their type, is marked by exudative lesions. The heaviest proteinuria was found in membraneous and membranoproliferative glomerulopathies. Changes in the serum creatinine and BUN levels indicative of a deteriorating renal function were noted in the membranoproliferative cases. The results are correlated with clinical observations of human glomerulopathies.
Animals↗