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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polyglandular autoimmune syndrome type II, (Schmidts syndrome), is defined as coexistence of two of the diseases: Addison's disease, insulin dependent diabetes mellitus and autoimmune thyroid disease. The first endocrine deficiency state typically develops after the age of twenty and in most cases it is Addison's disease. The prevalence is approximately 5 per 100,000. The syndrome occurs within families in half of the cases. The immunological mechanism is not finally determined, but both the humoral and cellular systems seem to be involved and furthermore there is an association with the major histocompatibility complex. Whereas treatment of the components in polyglandular autoimmune syndrome is straightforward, diagnosis may be troublesome: Patients with Addison's disease may be biochemically hypothyroid the first months of corticosteroid treatment. Patients with myxedema show decreased urine excretion of 17-ketosteroids until thyroid substitution treatment is sufficient. A decreased insulin requirement or increased frequency of hypoglycaemic attacks may be the first sign of an adrenocortical hypofunction in diabetic patients. Patients with one autoimmune disease and their relatives are predisposed to (other) autoimmune diseases.
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PMID:[Polyglandular autoimmune syndrome type II]. 260 41

Our understanding of HLA class II polymorphism has undergone a rapid evolution in the last few years. As in so many areas of modern biology, this progress has depended largely on the application of recombinant DNA techniques to the study of this gene family. In particular, the recent development of methods of gene amplification by means of the polymerase chain reaction has allowed for the rapid assessment of polymorphism in the human population. In addition, the elucidation by x-ray crystallographic analysis of the three-dimensional structure of an HLA molecule has been a major step. These areas of progress have now begun to converge to allow a more detailed approach to the problem of class II polymorphism and disease susceptibility. As discussed in this review, the data so far indicate that a few amino acid substitutions in class II molecules may exert a critical influence on susceptibility to autoimmune diseases such as RA and IDDM. The mechanism by which these class II polymorphisms predispose to autoimmune disease is still unknown. It is tempting to speculate that differences in the binding affinity of HLA molecules for autoantigens might be involved; however, as yet no specific autoantigen has been identified for either RA or IDDM. Intriguingly, sequence similarities have been observed between some viral proteins and class II molecules, raising the possibility that these infectious agents might induce autoimmunity by "molecular mimicry." Examples include the human cytomegalovirus protein, IE2 as well as the Epstein Barr virus gp110 protein. Other possible mechanisms involve more complex immunoregulatory effects, such as the absence of suppressor functions that appear to be under the influence of the HLA genes. To some extent, the persistent ignorance about the cause of autoimmunity reflects a general lack of knowledge concerning exactly how HLA polymorphisms exert immunoregulatory effects. For example, in addition to influencing antigen presentation, MHC molecules also affect the overall T cell repertoire during thymic selection. The relative importance of HLA class II polymorphism in exerting immunoregulatory effects by means of thymic selection of the T cell repertoire is unknown. For autoimmune diseases such as RA and IDDM, there is a need to identify a specific functional abnormality that is causing the disease before the etiological significance of the emerging associations with class II polymorphisms become clear.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:HLA class II polymorphism: implications for genetic susceptibility to autoimmune disease. 266 47

During the last 25 years the concept of a chronic autoimmune process leading to the development of insulin dependent diabetes (IDD) has emerged. The presence of two animal models for IDD, the BB rat and the NOD mouse, has improved our ability to understand the process leading to beta cell destruction. The hallmark of an autoimmune disease is the characteristic pathologic lesion of mononuclear infiltration of the pancreatic islets. Further histologic studies of the diabetic pancreas have identified the type of cells infiltrating the islets and led to the concept of pancreatic beta cells capable of presenting antigen. The initial description of linkage disequilibrium of HLA DR3 and DR4 alleles with IDD has now progressed to the molecular level with the identification of residue 57 of the HLA DQ beta chain as crucial to the genetic predisposition to IDD. Autoantibodies to cytoplasmic antigens (ICA), surface antigens, or a membrane protein of 64 kDa identified by immunoprecipitation, autoantibodies to secreted products such as insulin and proinsulin, and autoantibodies that are cytotoxic to cultured beta cells are islet specific autoantibodies that have been described. Some are probably only markers of immunologic activity; others might participate in the destruction itself. The use of ICA as a screening tool has been successful in identifying individuals prior to the onset of IDD. Widespread cellular immunological defects have been identified both in animal models and in man. In the BB rat, a seeming paradox of severe immunodeficiency occurs in an animal with autoaggressive destruction of beta cells. More subtle defects in immunoregulation have been described in the NOD mouse and in human IDD. The response of IDD in both animal models and in man to immunomodulation and to immunosuppression offers further evidence of an immunologically mediated disease. However, some therapies in the animal models, not typically considered immunologic, such as protein restriction and insulin therapy, have prevented IDD. The possibility of intervening prior to the onset of clinical disease at the level either of the initial process of recognition of the pancreatic beta cell as a target organ or of the effector mechanism is approaching a reality in human IDD.
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PMID:Insulin dependent diabetes mellitus, an autoimmune disorder? 267 79

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease whose notorious pathologic feature is insulitis accompanied by destruction of beta-cells. In this morphological study, we examined the pancreatic events during the onset of diabetes in spontaneously diabetic BB/Organon rats. Dendritic cells were the first cells to accumulate around the islets, followed by lymphocytes. Scavenger macrophages and MHC class II-positive beta-cells were only seen late in the disease. These observations suggest a role for antigen-presenting dendritic cells in the onset of the beta-cell-specific autoimmune reaction and emphasize the necessity to distinguish between the several monocyte-macrophage subtypes in studies on the pathogenesis of IDDM.
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PMID:Dendritic cells and scavenger macrophages in pancreatic islets of prediabetic BB rats. 268 15

Insulin-dependent diabetes mellitus (IDDM) has rarely, if ever, been reported to be an autoimmune disease associated with myasthenia gravis (MG). Two Chinese patients, one of whom was successfully treated with cyclosporin A (CyA) are reported, with discussion of pathophysiologic mechanisms involved and rationale for the treatment used.
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PMID:Myasthenia gravis and insulin-dependent diabetes mellitus in two adolescents. 279 20

The immunoglobulin fractions of serum from patients with spontaneous hyperinsulinaemic hypoglycaemia and others with type 1 diabetes stimulated insulin release both in islet-cell cultures and in vivo in rats. Serum from patients with type 2 diabetes, which is not an autoimmune disease, did not stimulate insulin release. The discovery of islet-cell-stimulating antibodies (ICSTA) completes for the islet the triad of autoantibodies (anticytoplasmic, antiproduct, and antireceptor) previously described in autoimmune thyroid disease. ICSTA may be important modulators of islet-cell secretion in man.
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PMID:Graves' disease of the beta cell: glucose dysregulation due to islet-cell stimulating antibodies. 290 75

The BB/W rat is currently the best model of type I (insulin dependent diabetes). Even though this rat develops an autoimmune disease, they are immune deficient. In this study we have demonstrated the almost complete absence of the OX 8+, OX 19+ T cytotoxic/suppressor population in diabetes prone and acute diabetic rats. This population is present in the diabetes resistant W line. The diabetes prone and acute diabetic rats have a relative increase in OX 8+, OX 19- natural killer (NK) cells. Our data suggests that virtually all OX 8+ cells in diabetes prone and acute diabetic animals are phenotypic NK cells.
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PMID:Deficiency of phenotypic cytotoxic-suppressor T lymphocytes in the BB/W rat. 293 80

Type 1 diabetes has been recognized as an organ-specific autoimmune disease. The NOD mouse showed a marked infiltration of T cells into the pancreatic islets and selectively destroyed B cells. The overt diabetes appeared in 90% of the females. Both T- and B-cell functions were markedly disturbed in the overt diabetes. Athymic NOD mice showed little incidence of insulitis. Some immunomodulators induced the overt diabetes. The NOD mouse has many similarities with diabetic profiles including biochemical, morphological, and immunological features of type 1 diabetes. Mice are familiar studies for genetic and immunological analyses. Therefore, the NOD mouse might be a useful model for elucidating etiopathogenesis of type 1 diabetes.
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PMID:The NOD mouse as a model of type I diabetes. 296 13

In this review we have summarized several lines of evidence supporting the concept that insulin dependent diabetes (IDDM) is an autoimmune disease. Initially, we have considered the association of IDDM with other autoimmune diseases, a fact that indirectly suggests involvement of the immune system. Other evidence implicating the immune system is the presence of auto-antibodies directed against pancreatic islet cells and cellular components of the immune system associated with pancreatic insulitis. Finally, we have examined the reported association of cell-surface proteins named histocompatibility antigens (HLA) with this particular disease. Structural and functional aspects of HLA have been considered along with regulatory mechanisms concerning the expression of these antigens.
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PMID:Insulin dependent diabetes mellitus as an autoimmune disease. 297 22

The development of IDDM correlates with the presence of biologic markers pointing to the involvement of the immune system in the disease process. In addition to clinical observations of association of IDDM with other autoimmune disease and morphologic evidence of a mononuclear cell infiltration of the islets of Langerhans at the onset of the disease, anti-islet cell antibodies are detected in the serum of IDDM patients. Moreover, a strong genetic association with HL-A DR3 and DR4 identifies a genetic background compatible with autoimmune phenomena. Whether autoimmune phenomena are primary or secondary to an initial damage of the islets by infectious agents or other environmental factors is unknown. Whether or not the autoimmune response participates in the selective destruction of insulin-secreting cells has been a major issue in the past five years. The presence of T lymphocytes and anti-islet cell antibodies, which selectively inhibit or lyse insulin-secreting cells in vitro, strongly suggests that it may be the case. A definitive demonstration is difficult to provide in human IDDM. The development of animal models for IDDM has allowed useful insight into the pathogenetic mechanisms responsible for IDDM. In both the BB rat and the low-dose streptozotocin mouse model, the role of the immune system in the destruction of the islets of Langerhans is supported by the prevention of the disease by treatments interfering with the immune system. The BB rat develops a spontaneous autoimmune disease on a genetic background defined by the association with a major histocompatibility complex allele without any evidence for a role in initial damage of islets of a triggering infectious or chemical process. The low-dose streptozotocin model is an autoimmune IDDM secondary to the selective damage of islet cells by a toxin. The present scheme of an islet cell target and specific autoreactive T and B lymphocyte clones raises two major issues: what is the target antigen on islet cells and what is the role at the molecular level of class II major histocompatibility complex genes in susceptibility for IDDM? The first issue is presently being addressed in several laboratories using the hybridoma technology. The second issue is addressed at the biochemical level by studying restriction site polymorphism of major histocompatibility genes in susceptible individuals and IDDM patients, and at the functional level by studying the action of monoclonal antibodies to class II antigen on the development of IDDM in animal models. These steps are likely to be a prerequisite to antigen-specific immunotherapy in IDDM.
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PMID:Autoimmune disorders in diabetes. 308 14


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