Changes in autoimmune thyroid disease following allogeneic bone marrow transplantation. (65/708)

Autoimmune diseases can be transmitted and eliminated by bone marrow transplantation (BMT). There have been several cases of autoimmune thyroid disease (AITD) occurring after BMT, but AITD remission has been rarely reported. We present four cases in which the remission or transfer of AITD occurred after an allogeneic BMT. Two patients with severe aplastic anemia (SAA) showed evidence of remission of Hashimoto's thyroiditis which they had before allogeneic BMT. One patient with SAA, which developed during treatment with propylthiouracil for Graves' disease, underwent allogeneic BMT and showed evidence of Graves' disease remission following BMT. In one patient, new AITD occurred after an allogeneic BMT from an HLA-matched sibling who already had AITD. These cases support the evidence that the immune system is newly reconstituted after BMT, and severe autoimmune disease can be an indication for BMT. To fully understand the real changes in autoimmune status after BMT, long-term prospective studies are necessary.  (+info)

Tripterygium wilfordii saponins and interleukin-10 prevent induction of experimental autoimmune thyroiditis by dendritic cells. (66/708)

AIM: To study the roles of Tripterygium wilfordii saponins (TII) and interleukin-10 (IL-10) on dendritic cells (DC)-induced experimental autoimmune thyroiditis (EAT). METHODS: We used mice as autoimmune thyroiditis model animals and divided them into 4 groups, namely DC group, TII group, IL-10 group, and control group. The level of thyroglobulin (Tg) antibody was assayed by ELISA. TNF beta production in the cultured supernatants and nitric oxide (NO) in the serum were measured by biological activation assay and Griess reaction, respectively. Tg-stimulated proliferation of lymphocytes was detected with MTT incorporation assay. The histopathological analysis of thyroid was carried out. RESULTS: Tg-pulsed DC were able to induce EAT with increase in the concentration of TgAb in serum and lymphocytes infiltration in thyroid. After treatment with TII or IL-10, DC could not induce EAT with lower levels of TgAb and no lymphocyte infiltration. The concentration of NO in serum, TNF beta activation, and the proliferation of lymphocytes in response to thyroglobulin in TII or IL-10 group were lower than those in DC group. CONCLUSION: TII and IL-10 are able to strongly inhibit the ability of DC to induce experimental autoimmune thyroiditis.  (+info)

The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection. (67/708)

BACKGROUND/AIMS: The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection. METHODS: The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4-5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progression, psychosocial impact of HCV infection, extrahepatic manifestations, and HLA class II associations. RESULTS: The most common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women fell within the clinical range for psychological distress. A history of icteric hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women after inoculation (p=0.002). The mean histological activity index/fibrosis scores of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15 (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex, positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%, 3.8%, and 3.8%. CONCLUSIONS: A benign course of HCV infection with lack of disease progression was observed in women with chronic HCV, 22 years after inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated with viral clearance. Despite this favourable outcome, high levels of psychological distress and poor quality of life were present.  (+info)

Fas and Bcl-2 protein expression in thyrocytes of patients with nodular goiter. (68/708)

OBJECTIVE: The relative expression of the apoptotic protein Fas and the anti-apoptotic protein Bcl-2 were investigated in thyrocytes from patients with non-toxic nodular goiter (NTG, n=20) and Hashimoto's thyroiditis (HT, n=5), who underwent fine-needle aspiration biopsy for diagnostic reasons. On the basis of the clinical and cytological findings, the patients with NTG were sub-classified into the group of those with colloid nodules (n=9), degenerative nodules (n=6) and adenomatous nodules (n=5). METHODS: Fine-needle biopsy aspirates were examined by immunocytochemistry for Fas and Bcl-2 expression, using specific monoclonal antibodies. For the evaluation of Fas and Bcl-2 immuno-reactivity, an expression index, based on the number of cells with positive staining, was used: grade 1 included samples with positive staining in <20% of cells; grade 2 included samples with 20-50% positive cells; and grade 3 included samples with >50% positive cells. RESULTS: Fas protein expression was generally low (grade 1) in patients with nodular goiter, in contrast to patients with HT, in whom high expression was detected (grade 3). Only in aspirates from degenerative nodules (four out of six), and in which lymphocytes were also present, was Fas expressed at an intermediate level (grade 2). On the other hand, Bcl-2 protein was differentially expressed among the nodule subtypes. It was low in colloid and degenerative nodules (grade 1) but high in adenomatous ones (grades 2 and 3). Bcl-2 expression was also low in patients with HT (grade 1). CONCLUSION: It is concluded that in comparison to HT, where there is up-regulation of Fas and down-regulation of Bcl-2 protein, Fas expression is low in human goiter, indicating low apoptotic activity. The regulation of Bcl-2 protein differs between adenomatous and colloid nodules, suggesting that this protein may play a role in the differentiation of thyroid nodules.  (+info)

Expression of ICAM-1, B7.1 and TPO on human thyrocytes induced by IFN-alpha. (69/708)

OBJECTIVE: To detect expression of intercellular adhesion molecule-1 (ICAM-1), B7.1 and thyroid peroxidase (TPO) on thyrocyte and study the possible mechanism of interferon-alpha (IFN-alpha) in the pathogenesis of autoimmune thyroid disease (AITD). METHODS: Thyrocytes were cultured from 6 normal persons. Antigen expression on thyrocytes induced by cytokines was examined using immunofluorescence staining with flow cytometer. RESULTS: IFN-alpha significantly stimulated the expression of ICAM-1, B7.1 and TPO, as compared with those of control group. IFN-gamma markedly enhanced the expression of HLA-DR and ICAM-1, but not B7.1. Prolactin (PRL) resulted in increased expression of ICAM-1, B7.1, as well as overexpression of TPO, which is more significant than that stimulated by IFN-alpha. CONCLUSIONS: Thyroid autoimmunity induced by IFN-alpha is associated with the expression of ICAM-1, B7.1 and TPO. IFN-gamma could not induce the expression of B7.1, therefore it is not an initiator in AITD. In addition, we should pay more attention to PRL which possibly plays an important role in the initiation and perpetuation of postpartum thyroiditis.  (+info)

Expression of CD40 and apoptosis related molecules in autoimmune thyroid diseases. (70/708)

Apoptosis is responsible for the loss of thyrocytes in autoimmune thyroiditis. Recent investigations into the pathogenesis of apoptosis have revealed that the important roles of suicide molecules expression on both thyrocytes and cytotoxic T-lymphocytes. To study the mechanism of thyrocyte loss in various forms of thyroiditis, we evaluated in situ expression patterns of CD40, Fas, and Fas-L on thyrocytes and infiltrating inflammatory cells by immunohistochemical staining of thyroid samples obtained from 49 patients (Graves' disease, n=10: Hashimoto's thyroiditis, n=14; nonspecific lymphocytic thyroiditis, n=11; subacute granulomatous thyroiditis, n=11; normal, n=3). The role of cytotoxic T-lymphocytes was also evaluated by analyzing the expression of granzyme B along with their phenotypic characteristics. CD40 was not expressed on thyrocytes of normal controls while they showed a diffuse expression of Fas and a scattered focal expression of Fas-L. The plump thyrocytes proximal to the inflammatory infiltrates showed more intense expressions of these three molecules in various forms of thyroiditis and a close correlation was found between CD40 and Fas-L expression on thyrocytes. Unlike Fas, which was expressed on infiltrating lymphocytes in all groups, Fas-L was not expressed on infiltrating lymphocytes, except those in subacute granulomatous thyroiditis. Granzyme B expressing activated cytotoxic T-lymphocytes occupied a negligible proportion of CD8+ T-lymphocytes in various forms of thyroiditis, and no difference was found in terms of their proportions according to the type of thyroiditis. These results show the acquisition of CD40, Fas and Fas-L molecules on thyrocytes proximal to inflammatory cell aggregates and the negligible expression of granzyme B and Fas-L on the infiltrating lymphocytes, and suggest that Fas and Fas-L mediated apoptosis of thyrocytes (fratricide) may be more important than T cell-mediated cytotoxicity in various forms of thyroiditis.  (+info)

Hashimoto's encephalopathy: documentation of mesial temporal seizure origin by ictal EEG. (71/708)

Hashimoto's encephalopathy is a chronic relapsing and remitting encephalopathy associated with antithyroid antibodies. Seizures are a frequent manifestation, but are not well characterized in the literature with respect to their onset. We describe a 48-year-old patient with recurrent encephalopathy and seizures, and elevated antithyroid antibodies. One seizure was documented with video-EEG monitoring using scalp and sphenoidal electrodes. The ictal discharge originated in the left mesial-basal temporal region. MRI showed an increased T2 signal in the white matter of the centrum semiovale, but no temporal pathology. Symptoms resolved after treatment with prednisone and azathioprine. Hashimoto's encephalopathy should be considered in patients with unexplained encephalopathy and seizures, including those originating in the temporal lobe.  (+info)

Expression and regulation of Fas and Fas ligand on thyrocytes and infiltrating cells during induction and resolution of granulomatous experimental autoimmune thyroiditis. (72/708)

Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced by mouse thyroglobulin-sensitized spleen cells activated in vitro with mouse thyroglobulin, anti-IL-2R, and IL-12. G-EAT lesions reach maximal severity 19-21 days after cell transfer, and lesions almost completely resolve by day 35. Depletion of CD8+ cells delays resolution and reduces Fas ligand (FasL) mRNA expression in thyroids. This study was undertaken to analyze Fas and FasL protein expression in the thyroid during induction and resolution of G-EAT and to determine whether CD8+ cells might regulate Fas or FasL expression in the thyroid. Fas and FasL expression was analyzed by immunohistochemical staining or in situ hybridization in thyroids of mice with or without depletion of CD8+ cells. Fas and FasL proteins were not detectable in normal thyroids, but expression of both proteins increased during development of G-EAT. Fas was expressed primarily by inflammatory cells; some enlarged thyrocytes were also Fas+. Thyrocytes had intense FasL immunoreactvity, and many CD8+ cells were also FasL positive. Depletion of CD8+ cells resulted in decreased FasL expression by thyrocytes and inflammatory cells, but had no effect on Fas expression. TUNEL assay detected many apoptotic inflammatory cells in proximity to thyrocytes. CD8-depleted thyroids had ongoing inflammation with fewer apoptotic infiltrating cells at day 35. Administration of a neutralizing anti-FasL mAb had no apparent effects on development of G-EAT, but anti-FasL was as effective as anti-CD8 in preventing G-EAT resolution. These results suggested that CD8+ T cells and thyrocytes may kill inflammatory cells through the Fas pathway, contributing to G-EAT resolution.  (+info)