Expression of cytokeratin 20 in thyroid carcinomas and peripheral blood detected by reverse transcription polymerase chain reaction.
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We investigated a nested reverse transcriptase polymerase chain reaction (RT-PCR) system to detect CK20 mRNA in thyroid carcinomas, benign thyroid diseases and peripheral blood to improve diagnosis of thyroid carcinoma and to detect disseminated tumour cells. Frozen tissue samples of 46 thyroid carcinomas and 30 benign thyroid diseases (14 multinodular goiters, 14 follicular adenomas, two Hashimoto's thyroiditis) were obtained intraoperatively. Preoperative blood samples were drawn from 31 patients with thyroid cancer, nine patients with benign thyroid disorders and 20 healthy volunteers. Nine out of nine medullary, 9/12 follicular, 7/19 papillary and 2/6 anaplastic carcinomas expressed CK20 transcripts. CK20 mRNA was undetectable in 30 tissue sections of benign thyroid diseases. Circulating tumour cells were found in the blood of 3/8 patients with medullary carcinoma, 2/8 patients with follicular carcinoma, 2/11 patients with papillary carcinoma and 1/4 patients with an anaplastic carcinoma. Nine blood samples of patients with benign thyroid diseases and 20 healthy volunteers tested negative. For the first time CK20 mRNA could be detected in tissue sections of thyroid carcinomas and peripheral blood samples of patients with thyroid cancer. It was not detectable in benign thyroid diseases. Our results therefore strongly suggest that CK20 RT-PCR assays may improve the diagnosis of thyroid carcinoma and is able to detect circulating tumour cells in peripheral blood of thyroid carcinoma patients. (+info)
Transgenic expression of Fas ligand on thyroid follicular cells prevents autoimmune thyroiditis.
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"Immune privilege" is defined as tissue resistance to aggression by specifically activated lymphocytes, and involves the interaction between Fas expressed on infiltrating cells and Fas ligand (FasL) constitutively expressed on the target tissue. To test whether ectopic expression of FasL on thyrocytes could prevent autoimmune aggression of the thyroid by activated lymphoid cells, three lines of transgenic mice expressing low, intermediate, and high levels of functional FasL on thyroid follicular cells were generated. Experimental autoimmune thyroiditis was induced by immunization with mouse thyroglobulin. In all of the experiments, the effects were dependent on the level of FasL expression. Low and intermediate expression had no or only weak preventive effects, respectively, whereas high FasL expression strongly inhibited lymphocytic infiltration of the thyroid. Anti-mouse thyroglobulin-proliferative and cytotoxic T cell responses, as well as autoantibody production, were diminished in transgenic mice expressing high levels of FasL relative to controls. Furthermore, in these latter mice Th1 responses to mouse thyroglobulin were profoundly down-regulated, uncovering a new potential role for FasL in peripheral tolerance to organ-specific Ags. In sum, the prevention of experimental autoimmune thyroiditis by FasL on thyrocytes is dependent on the level of FasL expression. (+info)
A case of Hashimoto's thyroiditis with markedly elevated serum thyroglobulin and evidence of its influence on the measurement of anti-thyroglobulin antibody by highly sensitive assays.
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We present the case of a 66-year-old woman with Hashimoto's thyroiditis, who showed extremely high concentrations of serum thyroglobulin (Tg). Serum Tg levels were markedly elevated following a slight elevation of serum thyrotropin (TSH) (22,000 ng/mL and 11.1 microU/mL, respectively). Although elevated concentrations of serum Tg declined concomitant with decrease of serum TSH one month later, Tg concentrations remained high (> 948 ng/mL) even at normal or suppressed TSH levels. There was no evidence of massive thyroid tissue damage or thyroid tumor. To our knowledge, there have been no case reports of such high concentrations of serum Tg (> 2 x 10(4) ng/mL) in the clinical course of Hashimoto's thyroiditis. Furthermore, we showed evidence that extremely high Tg levels could possibly influence the measurement of anti-Tg autoantibody using highly sensitive radioimmunoassays. (+info)
Hypothyroidism in transgenic mice expressing IFN-gamma in the thyroid.
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IFN-gamma has been implicated with contradictory results in the pathogenetic process of autoimmune (Hashimoto's) thyroiditis, the most common cause of hypothyroidism in adults. To test whether the local production of IFN-gamma can lead to thyroid dysfunction, we have generated transgenic mice that express constitutively IFN-gamma in the thyroid follicular cells. This expression resulted in severe hypothyroidism, with growth retardation and disruption of the thyroid architecture. The hypothyroidism derived from a profound inhibition of the expression of the sodium iodide symporter gene. Taken together, these results indicate a direct role of IFN-gamma in the thyroid dysfunction that occurs in autoimmune thyroiditis. (+info)
Thyroiditis: differential diagnosis and management.
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Thyroiditis is a group of inflammatory thyroid disorders. Patients with chronic lymphocytic thyroiditis (also referred to as Hashimoto's thyroiditis) present with hypothyroidism, goiter, or both. Measurement of serum thyroid autoantibodies and thyroglobulin confirms the diagnosis. Subacute granulomatous thyroiditis (sometimes referred to as de Quervain's disease) is a self-limited but painful disorder of the thyroid. Physical examination, elevated erythrocyte sedimentation rate, elevated thyroglobulin level and depressed radioactive iodine uptake (RAIU) confirm the diagnosis. Subacute lymphocytic thyroiditis (silent thyroiditis) is considered autoimmune in origin and commonly occurs in the postpartum period. Symptoms of hyperthyroidism and depressed RAIU predominate. Acute (suppurative) thyroiditis is a rare, infectious thyroid disorder caused by bacteria and other microbes. The rare, invasive fibrous thyroiditis (Riedel's thyroiditis) presents with a slowly enlarging anterior neck mass that is sometimes confused with a malignancy. (+info)
Circulating concentrations of soluble L-selectin (CD62L) in patients with primary Sjogren's syndrome.
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OBJECTIVE: Serum concentrations of soluble (s) L-selectin (CD62L) were measured in patients with primary Sjogren's syndrome (SS) to relate these concentrations to clinical and immunological features of SS. METHODS: The study included 40 consecutive patients (38 women and two men) with a mean age of 61 years (range 24-78) who fulfilled four or more of the preliminary diagnostic criteria for SS proposed by the European Community Study Group in 1993, and 33 healthy blood donors from the hospital blood bank. A sandwich enzyme linked immunosorbent assay (ELISA) was used to detect the soluble form of human sL-selectin (CD62L). RESULTS: The mean (SEM) values of sL-selectin (CD62L) were 861 (66) microg/ml for patients with SS and 986 (180) microg/ml for healthy blood donors, but there was no significant difference. In patients with primary SS, serum sL-selectin (CD62L) concentrations were significantly higher in patients with Raynaud's phenomenon (1275 (112) microg/ml versus 789 (69) microg/ml, p=0.007), autoimmune thyroiditis (1162 (113) microg/ml versus 787 (69) microg/ml, p=0.02) and rheumatoid factor (993 (95) microg/ml versus 684 (70) microg/ml, p=0.01) when compared with patients without these features. CONCLUSION: The presence of Raynaud's phenomenon, autoimmune thyroiditis and rheumatoid factor is associated with higher concentrations of circulating sL-selectin (CD62L) in the sera of patients with primary SS. (+info)
Evidence for a new Graves disease susceptibility locus at chromosome 18q21.
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Graves disease (GD) is a common autoimmune thyroid disorder that is inherited as a complex multigenic trait. By using a single microsatellite marker at each locus, we screened the type 1 diabetes loci IDDM4, IDDM5, IDDM6, IDDM8, and IDDM10 and the fucosyltransferase-2 locus for linkage in sib pairs with GD. This showed a two-point nonparametric linkage (NPL) score of 1.57 (P=.06) at the IDDM6 marker D18S41, but NPL scores were <1.0 at the other five loci. Thus, the investigation of the IDDM6 locus was extended by genotyping 11 microsatellite markers spanning 48 cM across chromosome 18q12-q22 in 81 sib pairs affected with autoimmune thyroid disease (AITD). Multipoint analysis, designating all AITD sib pairs as affected, showed a peak NPL score of 3.46 (P=.0003), at the marker D18S487. Designation of only GD cases as affected (74 sib pairs) showed a peak NPL score of 3.09 (P=.001). Linkage to this region has been demonstrated in type 1 diabetes (IDDM6), rheumatoid arthritis, and systemic lupus erythematosus, which suggests that this locus may have a role in several forms of autoimmunity. (+info)
Cutting edge: a soluble form of CTLA-4 in patients with autoimmune thyroid disease.
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We have recently identified a novel transcript of the CTLA-4 gene that may represent a native soluble form of CTLA-4 (sCTLA-4). To determine whether sCTLA-4 was expressed in humans, we applied a sensitive enzyme immunoassay on serum from patients with autoimmune thyroid disease (ATD). Eleven of 20 patients with ATD had circulating levels of sCTLA-4 ranging from 28 to 78 ng/ml, whereas only 1 of 30 apparently healthy volunteers had a level greater than 4 ng/ml. sCTLA-4 immunoreactivity was inhibited by its binding to B7.1, suggesting that sCTLA-4 is a functional receptor. Immunoprecipitation analysis of serum from patients with ATD revealed a polypeptide consistent with the predicted size of sCTLA-4. We conclude that a native soluble form of CTLA-4 is derived from an alternate transcript of the CTLA-4 gene, and its level in plasma is elevated among a population of patients with ATD. (+info)