(1/708) Peripheral autoantigen induces regulatory T cells that prevent autoimmunity.

Previous studies have shown that autoimmune thyroiditis can be induced in normal laboratory rats after thymectomy and split dose gamma-irradiation. Development of disease can be prevented by reconstitution of PVG rats shortly after their final irradiation with either peripheral CD4(+)CD45RC- T cells or CD4(+)CD8(-) thymocytes from syngeneic donors. Although the activity of both populations is known to depend on the activities of endogenously produced interleukin 4 and transforming growth factor beta, implying a common mechanism, the issue of antigen specificity of the cells involved has not yet been addressed. In this study, we show that the regulatory T cells that prevent autoimmune thyroiditis are generated in vivo only when the relevant autoantigen is also present. Peripheral CD4(+) T cells, from rats whose thyroids were ablated in utero by treatment with 131I, were unable to prevent disease development upon adoptive transfer into thymectomized and irradiated recipients. This regulatory deficit is specific for thyroid autoimmunity, since CD4(+) T cells from 131I-treated PVG.RT1(u) rats were as effective as those from normal donors at preventing diabetes in thymectomized and irradiated PVG.RT1(u) rats. Significantly, in contrast to the peripheral CD4(+) T cells, CD4(+)CD8(-) thymocytes from 131I-treated PVG donors were still able to prevent thyroiditis upon adoptive transfer. Taken together, these data indicate that it is the peripheral autoantigen itself that stimulates the generation of the appropriate regulatory cells from thymic emigrant precursors.  (+info)

(2/708) Insulin dependent diabetes mellitus (IDDM) and autoimmune thyroiditis in a boy with a ring chromosome 18: additional evidence of autoimmunity or IDDM gene(s) on chromosome 18.

A 4 year 3 month old boy with insulin dependent diabetes mellitus (IDDM), autoimmune thyroiditis, slight mental retardation, facial dysmorphism, and a de novo ring chromosome 18 (deletion 18q22.3-18qter) is described. This unique association of defects could represent a chance association. Alternatively, the clinical features could be the result of the chromosomal aberration. If so, one could speculate that a gene or genes on chromosome 18 might act as a suppressor or activator of the autoimmune process by itself or in concert with other IDDM loci.  (+info)

(3/708) Pseudogout attack associated with chronic thyroiditis and Sjogren's syndrome.

A 66-year-old woman, diagnosed with chronic thyroiditis at age 63, presented with anorexia and fatigue. Therapy for the chronic thyroiditis consisted of levothyroxine sodium (100 microg/day). Her symptoms were attributed to the insufficient supply of levothyroxine sodium. Following a dosage increase to 150 microg/day, she suffered from an acute attack of pseudogout. Clinical features were complicated by Sjogren's syndrome, which appeared after treatment onset. Pseudogout was effectively treated by colchicine after administration of diclofenac sodium failed to alleviate the symptoms. Pseudogout is a recognized complication of thyroid replacement therapy, but association with Sjogren's syndrome has not been previously reported.  (+info)

(4/708) Hashimoto's encephalitis as a differential diagnosis of Creutzfeldt-Jakob disease.

OBJECTIVES: During an epidemiological study of Creutzfeldt-Jakob disease in Germany, Hashimoto's encephalitis was encountered as a differential diagnosis, which has not yet been described in this context. METHODS: The symptoms and findings of seven patients who fulfilled the criteria for "possible" Creutzfeldt-Jakob disease are presented. RESULTS: A Hashimoto's thyroiditis with antibodies against thyroglobulin or thyroid peroxidase, or both and a hypoechoic thyroid ultrasonogram were found in all cases. Analysis of CSF disclosed an increased leucocyte count in three patients, and a raised CSF:serum concentration ratio of albumin (QA1b) in four patients. The 14-3-3 protein, typical of Creutzfeldt-Jakob disease, could not be detected in any of our patients. No periodic sharp wave complexes, which are typical of Creutzfeldt-Jakob disease, were detected on EEG in any of the cases. By contrast with Creutzfeldt-Jakob disease, which leads to death within a few months, the patients with Hashimoto's encephalitis often recover quickly when treated adequately. All the patients improved after administration of corticosteroids. CONCLUSION: The clinical symptomatology of both diseases may be very similar: dementia, myoclonus, ataxia, and personality change or psychotic phenomena are characteristic symptoms.  (+info)

(5/708) A new rapid technique for the fixation of thyroid gland surgical specimens.

One of the main diagnostic problems in thyroid pathology is to distinguish between follicular adenoma and follicular carcinoma. Thorough sampling of the nodule's capsule is recommended in order to identify capsular invasion. However, during the hardening of the tissue, by the usual fixatives the capsule shrinks and rolls downwards and sometimes the capsule separates from the remaining tissue. The present work evaluates the use of "Lymph Node Revealing Solution" (LNRS) for the rapid fixation (2h) of different thyroid lesions as compared to that of formalin. Fifty-one unselected consecutive cases of thyroid nodules, which included various benign and malignant lesions, were examined. Each specimen was cut in two equal parts; one was fixed in LNRS, the other in formalin. Fixation in LNRS for 2 hours gave adequate results in sectioning and staining of the tissue, and excellent immunostains. Its advantage over formalin is the conservation of the natural relationship between the capsule and the rest of the tissue, on the same plane, as well as the short time required for the final diagnosis.  (+info)

(6/708) Apoptosis in the effector phase of autoimmune diabetes, multiple sclerosis and thyroiditis.

The immune system is unusual in two respects. It produces billions of new cells daily that traffic throughout the body and cells within the system proliferate rapidly following exposure to an infectious agent. Both of these attributes require that cell production be regulated by cell death. Human diseases characterized by accelerated cell death leading to immunodeficiency disorders or by reduced cell death leading to systemic autoimmune diseases have been identified. In certain autoimmune diseases, the immune system directs its powerful cytotoxic effector mechanisms against specialized cells such as oligodendrocytes in multiple sclerosis, the beta cells of the pancreas in diabetes mellitus and thyrocytes in Hashimoto's thyroiditis. In this review, we examine the cytotoxic effector pathways implicated in cell death in organ specific autoimmune disorders.  (+info)

(7/708) Development of an animal model of autoimmune thyroid eye disease.

In previous studies we have transferred thyroiditis to naive BALB/c and NOD mice with human thyrotropin (TSH) receptor (TSHR)-primed splenocytes. Because the TSHR has been implicated in the pathogenesis of thyroid eye disease (TED) we have examined the orbits of recipients of TSHR-primed T cells, generated using a TSHR fusion protein or by genetic immunization. In the NOD mice, 25 of 26 animals treated with TSHR-primed T cells developed thyroiditis with considerable follicular destruction, numerous activated and CD8+ T cells, and immunoreactivity for IFN-gamma. Thyroxine levels were reduced. Thyroiditis was not induced in controls. None of the NOD animals developed any orbital pathology. Thirty-five BALB/c mice received TSHR-primed spleen cells. Thyroiditis was induced in 60-100% and comprised activated T cells, B cells, and immunoreactivity for IL-4 and IL-10. Autoantibodies to the receptor were induced, including TSH binding inhibiting Igs. A total of 17 of 25 BALB/c orbits displayed changes consisting of accumulation of adipose tissue, edema caused by periodic acid Schiff-positive material, dissociation of the muscle fibers, the presence of TSHR immunoreactivity, and infiltration by lymphocytes and mast cells. No orbital changes or thyroiditis were observed in control BALB/c mice. We have induced orbital pathology having many parallels with human TED, only in BALB/c mice, suggesting that a Th2 autoimmune response to the TSHR may be a prerequisite for the development of TED.  (+info)

(8/708) Involvement of epitope mimicry in potentiation but not initiation of autoimmune disease.

We have examined whether the peptide (368-381) from the murine adenovirus type 1 E1B sequence, exhibiting a high degree of homology with the known pathogenic thyroglobulin (Tg) T cell epitope (2695-2706), can induce experimental autoimmune thyroiditis (EAT) in SJL/J mice. The viral peptide was a poor immunogen at the T or B cell level and did not elicit EAT either directly or by adoptive transfer assays. Surprisingly, however, the viral peptide was highly antigenic in vitro, activating a Tg2695-2706-specific T cell clone and reacting with serum IgG from mice primed with the Tg homologue. The viral peptide also induced strong recall responses in Tg2695-2706-primed lymph node cells, and subsequent adoptive transfer of these cells into naive mice led to development of highly significant EAT. These data demonstrate that nonimmunogenic viral peptides can act as agonists for preactivated autoreactive T cells and suggest that epitope mimicry may at times play a potentiating rather than a precipitating role in the pathogenesis of autoimmune disease.  (+info)