Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied 25 patients with polyglandular autoimmune disease with respect to HLA antigens. Whereas the combination of insulin dependent diabetes with Graves' disease or atrophic thyroiditis was associated with an increase in HLA-B8, this was not found to be the case for patients with I.D.D.M. and goitrous thyroiditis. However 4/7 of these patients were DRw3 positive in contrast to previously established normal distribution of HLA-B8 in patients with goitrous thyroiditis alone. These data suggest that patients with polyglandular failure may be highly selected for HLA-B8/DRw3 positivity. We also report on two families with polyglandular autoimmune disease; the results suggest that these disorders are not necessarily transmitted with B8/DRw3 bearing haplotypes. In one family both the affected mother and non-affected father were B8 positive. The mother's B8, which was associated with DRw7, BfF and Rga did not appear to be involved in the transmission of disease susceptibility to two affected offspring. The search for complete haplotypic arrangement should be pursued to see whether this uncommon haplotype arrangement is peculiar to autoimmune diseases.
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PMID:Polyglandular autoimmune disease and HLA. 700 51

Stored sera from 466 patients with insulin-dependent diabetes mellitus and from 144 controls were examined for organ-specific antibodies to human adrenal cortex. Adrenal antibodies were found in seven of the patients with IDDM (1.5%) and in one control (0.7%). None of 91 black patients with IDDM had adrenal antibodies. All of the seven patients with adrenal antibodies had other organ-specific antibodies. Three had clinical hypothyroidism and one was thyrotoxic. All of these seven patients had a HLA-B8-bearing haplotype, suggesting that the B8-bearing haplotype confers an extremely high "relative risk" for adrenal autoimmunity in IDDM. Organ-specific autoimmune disease and/or organ-specific antibodies were found in 30% of the first-degree relatives of these eight probands with the adrenal antibodies (seven with IDDM and one control). We conclude that screening patients with IDDM for adrenal antibodies of low yield (1.9% among white patients). Further, adrenal antibodies may be present for at least two years without the development of Addison disease. Antibodies reactive only to the zona glomerulosa of the adrenal cortex may be benign. Patients with IDDM and thyroid microsomal antibodies are more likely to have adrenal antibodies (6.5%), as are patients with IDDM and a B8-bearing haplotype and those with IDDM and family histories of organ-specific autoimmunity.
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PMID:Adrenal autoantibodies and Addison disease in insulin-dependent diabetes mellitus. 740 Aug 84

Insulin-dependent diabetes mellitus type 1 is an autoimmune disease of pancreatic beta-cells with a certain genetic predisposition that is not yet clear. In spite of the confirmed association of diabetes mellitus type 1 with several HLA haplotypes it is considered that other loci must be involved for total genetic susceptibility to the disease. The relationship of insulin deficiency and decreased pancreatic amylase activity suggests that insulin itself is a direct activator of amylase gene expression. Endocrine pancreatic function was monitored by the indirect non-invasive method of urinary pancreatic amylase activity determination (expressed in percentage of total amylase activity) in diabetic children, their parents, healthy sisters and brothers, and in a separate group of women with diabetes type 1 of over 20 years duration. The incidence of hereditary amylase polymorphism variants in these subjects was also ascertained. Decreased pancreatic amylase activity in urine (under 58%) was found to be a characteristic trait in diabetics, and a susceptibility trait in asymptomatic family members. Normal pancreatic amylase activity (66.7 +/- 5.4%) is rare in diabetic patients type 1, but may be seen as a favourable prognostic trait, representing resistance to diabetic complications. The results support the suggestion that hereditary predisposition to the disease is inherited from the father rather than the mother, and that heterozygous amylase polymorphism variants protect their carriers against diabetes mellitus type 1.
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PMID:Urinary amylase isoenzymes and amylase polymorphism variants in families with diabetes mellitus type 1. 750 71

By using an immunoprecipitation assay, we analysed reactivity of autoantibodies to human recombinant GAD65 and GAD67 in sera from patients with autoimmune polyendocrine syndrome Type II (APS II) with and without Type 1 (insulin-dependent) diabetes mellitus (IDDM) compared to patients with organ-specific autoimmunity. Overall antibodies to GAD65 were correlated with IDDM in all study groups, whereas GAD67 antibodies were associated with IDDM when APS II coexists. Antibodies to GAD65 and GAD67 were detected in 13 (44.8%) and 7 (24.1%) out of 29 APS II patients with IDDM, but in only 4 (13.8%) and 2 (6.9%) out of 29 APS II patients without IDDM, respectively (p < 0.05). In short-standing IDDM (< 1 year), antibodies to GAD67 were significantly more frequent in patients with APS II (5 of 9 [55.6%] subjects) compared to matched diabetic patients without coexisting polyendocrinopathy (1 of 18 [5.6%] subjects) (p < 0.02). The levels of GAD65 (142 +/- 90 AU) and GAD67 antibodies (178 +/- 95 AU) were significantly higher in patients with polyglandular disease than in patients with isolated IDDM (91 +/- 85 AU and 93 +/- 57 AU) (p < 0.02). Interestingly, all 11 GAD67 antibody positive subjects also had GAD65 antibodies (p < 0.0001), and in 10 of 11 anti-GAD67 positive sera the GAD67 antibodies could be blocked by either GAD67 or GAD65, suggesting the presence of cross-reactive autoantibodies. No correlation was observed between GAD antibodies and age, sex or any particular associated autoimmune disease, besides IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association between antibodies to the MR 67,000 isoform of glutamate decarboxylase (GAD) and type 1 (insulin-dependent) diabetes mellitus with coexisting autoimmune polyendocrine syndrome type II. 757 49

Insulin-dependent diabetes mellitus (IDDM) is considered to be an autoimmune disease. Autoimmune diseases result from the breakdown of self-tolerance elicited by environmental factors on a susceptible genetic background. This reduced tolerance allows immunocompetent cells to attack normal structures present on an individual's tissues. The study of the T cells present in the islets of patients who died at the onset of the disease allowed the recognition of "superantigens" as etiopathogenetic factors in the development of IDDM. Since superantigens are the product of bacteria or viruses able to quickly stimulate a large number of the peripheral T cells sharing the same T cell receptor V beta segments once presented by certain HLA class II molecules, a number of observations in genetics, immunology, virology and epidemiology can now find a unifying explanation.
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PMID:Exposure to superantigens as an immunogenetic explanation of type I diabetes mini-epidemics. 758 94

This chapter aims to describe ways in which autoimmunity can be prevented or reversed and 'self-tolerance' re-established. To this end we have largely restricted our overview to the two main autoimmune disease models with which we are involved, i.e. IDDM in NOD mice and EAT in H-2k mice although, where appropriate and to demonstrate a particular point, other models are mentioned. The chapter has been divided into sections covering protection afforded by 1) transgenes, 2) autoantigen and 3) by reagents targetting T-cell surface molecules. Where established, the mechanism by which protection or tolerance is achieved is described but where, as in most cases, it is unknown the possibilities are discussed. Investigations using T-cell lines and clones and on islet regeneration which are currently being followed as part of a comprehensive approach to the study of autoimmunity are included as separate sections and their relevance discussed.
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PMID:Tolerance induction as a therapeutic strategy for the control of autoimmune endocrine disease in mouse models. 759 Aug 17

An association between insulin-dependent diabetes mellitus (type 1) and thyroid diseases has long been reported, but the morphological evaluation of the thyroid in type 1 diabetes patients without overt thyroid disease has always been limited to physical examination. Ultrasonography of the thyroid gland was performed in 45 patients with type 1 diabetes without overt thyroid disease, to study thyroid volume and the prevalence of thyroid nodules. Data were compared with those obtained in 45 age- and sex-matched control subjects residing in the same area. In the patients, thyroid volume had increased on average by 46%; 35% of male and 32% of female patients had a thyroid volume exceeding the 95% confidence limits of the matched controls. The prevalence of thyroid nodules was only slightly raised. On average, free thyroxine was increased in the presence of normal triiodothyronine levels. Four patients were frankly hyperthyroid. The patients also showed a higher prevalence of thyroid-microsomal antibodies, but the thyroid hormone status was not different in relation to thyroid volume, nor was thyroid volume in relation to the presence of autoantibodies. Patients with type 1 diabetes without overt thyroid disorders may have morphological, ultrasonographically detectable alterations of the thyroid gland, the expression of a possible involvement of the thyroid in an autoimmune disorder not limited to the islet cells.
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PMID:Thyroid volume in type 1 diabetes patients without overt thyroid disease. 761 18

Insulin-dependent (type 1) diabetes mellitus is an organ-specific autoimmune disease frequently associated with an islet-specific humoral autoimmune response. The role of islet cell autoantibodies in the disease process is unclear; in particular, it is not known whether they are a non-specific side effect of islet cell destruction or play a role in the autoimmune network leading to type 1 diabetes. Here we report the immunoglobulin gene usage and somatic mutation rates of a panel of seven human monoclonal islet cell autoantibodies (MICA 1-7) directed towards the major islet cell autoantigen glutamate decarboxylase (GAD). These autoantibodies were produced from cells from two patients with newly diagnosed type 1 diabetes. VH1, VH4 and V lambda 2 gene segments were frequently used in the MICA, but no correlation between V gene usage and epitope recognition was found. The nonrandom ratio of replacement versus silent mutations in the variable gene region, an accumulation of replacement mutations in the complementarity determining regions, which confer antigen binding, and the high relative avidity for GAD observed for MICA 1, 3, 4, and 6, suggested that the immune response to GAD is driven by the antigen. In contrast, MICA 2, 5, and 7, revealing a lower affinity for antigen, have accumulated a large number of silent mutations. These latter antibodies may, therefore, be characteristic for later stages of the chronic autoimmune disease. Our results argue in favor of an antigen-driven autoantibody response to islets in human type 1 diabetes. They suggest that GAD is an important target of autoimmunity associated with type 1 diabetes.
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PMID:Immunoglobulin variable gene analysis of human autoantibodies reveals antigen-driven immune response to glutamate decarboxylase in type 1 diabetes mellitus. 761 98

A 21-year-old patient, since the age of 16, presented a familial type of chronic autoimmune thrombocytopenia that responded only partially to various types of immunosuppressive treatment. His prolonged survival, compared to his decreased siblings, was complicated by the appearance of a severe enteropathy. High doses of corticosteroids induced a type 1 diabetes as a major side effect. The introduction of cyclosporine resulted in both a continuous complete clinical remission and a partial hematological remission and allowed the discontinuation of all other medication for 18 months. In uncommon complex autoimmune disease, cyclosporine may represent a safe and effective alternate therapy when other immunosuppressive agents have failed.
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PMID:Prolonged remission induced by cyclosporine in a patient with familial thrombocytopenia and enteropathy. 764 Jan 83

Insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice results from the T-lymphocyte-mediated destruction of the insulin-producing pancreatic beta-cells and serves as a model for human IDDM. Whereas a number of autoantibodies are associated with IDDM, it is unclear when and to what beta-cell antigens pathogenic T cells become activated during the disease process. We report here that a T-helper-1 (Th1) response to glutamate decarboxylase develops in NOD mice at the same time as the onset of insulitis. This response is initially limited to a confined region of glutamate decarboxylase, but later spreads intramolecularly to additional determinants. Subsequently, T-cell reactivity arises to other beta-cell antigens, consistent with intermolecular diversification of the response. Prevention of the spontaneous anti-glutamate decarboxylase response, by tolerization of glutamate decarboxylase-reactive T cells, blocks the development of T-cell autoimmunity to other beta-cell antigens, as well as insulitis and diabetes. Our data suggest that (1) glutamate decarboxylase is a key target antigen in the induction of murine IDDM; (2) autoimmunity to glutamate decarboxylase triggers T-cell responses to other beta-cell antigens, and (3) spontaneous autoimmune disease can be prevented by tolerization to the initiating target antigen.
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PMID:Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. 823 29


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