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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Induction of expression of MHC class II antigens on the surface of cells that do not ordinarily express these proteins has been implicated in the pathogenesis of autoimmunity in diabetes mellitus and autoimmune thyroiditis. Platelets express class I but not class II HLA antigens. In this report, we describe a child with acute idiopathic thrombocytopenic purpura who at the time of the thrombocytopenic episode had class II (HLA-DR) antigens on his platelets. Following recovery, the HLA-DR antigens were no longer present on the platelets. We postulated that class II had been induced on his megakaryocytes by a cytokine such as interferon gamma, and that the induced expression of class II antigens contributed to the autoimmune disorder. To substantiate this possibility we next studied class I and II antigen expression on an erythroleukaemia cell line (HEL), which has many megakaryocytic features. Following treatment of HEL cells with interferon gamma, class I expression was increased and HLA-DR antigens were induced. These observations suggest that cytokine-mediated induced HLA-DR expression may contribute to the pathogenesis of a subset of thrombocytopenias.
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PMID:HLA-DR expression by platelets in acute idiopathic thrombocytopenic purpura. 139 Feb 43

The Bio-Breeding (BB) rat develops spontaneous insulin-dependent diabetes mellitus (IDDM) and provides a useful animal model to study this human autoimmune disease. Treatment of BB rats with tumor necrosis factor (TNF) has been reported to prevent the development of IDDM. This suggests that deficient TNF production may be involved in the immunopathogenesis of autoimmune diabetes. In this study, we evaluated TNF production in diabetes-resistant (DR) BB rats, diabetes-prone (DP) BB rats, and DP BB rats protected from diabetes by the immunoadjuvant, complete Freund's adjuvant (CFA). TNF production in short-term cultures of peritoneal macrophages from DP rats was significantly less than that from control DR rats, both in the basal state and after stimulation with either interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS) in vivo and in vitro. In contrast, TNF production by macrophages from CFA-injected DP rats (basal and IFN-gamma or LPS-stimulated) was equal to or greater than that by macrophages from DP rats and similar to TNF production by macrophages from CFA-injected DR rats. These results suggest that development of autoimmune diabetes in BB rats may be causally related to deficient macrophage production of TNF, and that upregulation of TNF production may protect against diabetes development.
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PMID:Tumor necrosis factor production is deficient in diabetes-prone BB rats and can be corrected by complete Freund's adjuvant: a possible immunoregulatory role of tumor necrosis factor in the prevention of diabetes. 139 29

The development of T cell tolerance to self-antigens is imparted principally through negative selection events during thymic ontogeny. However, this tolerance may be limited to antigens that are expressed in the thymus, and additional mechanisms are probably required to regulate autoimmune responses to tissue-specific antigens. Autoimmune diabetes can be induced experimentally by treating susceptible stains of mice with multiple low doses of streptozotocin (STZ). In this report we show that transplantation of isolated islets of Langerhans into the thymuses of adult C57BL/KsJ mice will induce tolerance to the subsequent induction of autoimmune diabetes. This tolerance is tissue specific and thymus dependent. It was not induced by thymic transfer of adrenal tissue or by kidney transfer of islets. Furthermore, depletion of mature T cells was required and the tolerant state was abrogated by the adoptive transfer of normal splenocytes. It is interesting that pretreatment of the islets with STZ enhanced their ability to induce tolerance, and suggests that antigen shedding induced by tissue damage may facilitate transfer of islet antigens to tolerizing cells in the thymus. These findings indicate that thymic tolerance specific for tissue can be stimulated to occur in the presence of atopic tissue-specific intrathymic antigens. Elimination of disease-related T cells in the absence of global immunosuppression represents a novel approach for the prevention of autoimmune disease.
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PMID:Induction of tolerance to autoimmune diabetes with islet antigens. 140 56

Increased knowledge of the etiopathogenesis of Type 1 diabetes has focused great interest on the possibilities of preventing the disease. Type 1 diabetes is considered to be a chronic autoimmune disease characterized by gradual beta-cell destruction mediated by autoreactive T-lymphocytes during an asymptomatic prediabetic phase of varying duration. Both experimental and epidemiologic data indicate that nutritional cow milk exposure early in life may play a critical role in the initiation of beta-cell destruction. Accordingly a primary prevention study has been planned to test the hypothesis that dietary elimination of cow milk proteins over the first 9 months of life will decrease the subsequent risk of childhood type 1 diabetes in high risk infants. The possibility of identifying prediabetic individuals before decisive loss of beta-cell function by various islet cell-specific autoantibodies enables measures of secondary prevention in the prediabetic phase. There are indications from experimental and human studies that nicotinamide, a water-soluble group B vitamin, may be effective in preventing or delaying the presentation of diabetes. A European multicentre study will be initiated in the near future to explore whether oral nicotinamide can prevent or delay the clinical manifestation of Type 1 diabetes in high risk first degree relatives of diabetic children. We have to wait for the results of these intervention studies for years, and similarly other prevention strategies have to be tested in large-scale long-lasting clinical trials. Nevertheless, prevention of childhood diabetes may become a reality in the next century.
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PMID:[Can type-1 diabetes in children be prevented?]. 140 25

Nonobese diabetic (NOD) mice spontaneously develop a T-cell-mediated autoimmune disease that is similar in many respects to insulin-dependent diabetes mellitus in humans. NOD mice were shown to express major histocompatibility complex class I Kd and Db antigens. To examine the possible involvement of major histocompatibility complex class I molecules in the development of autoimmune insulitis, we attempted to express a different type of class I molecule in NOD mice by crossing C57BL/6 mice transgenic for the class I Ld gene with NOD mice. The backcross progeny expressed the Ld antigen on the peripheral blood lymphocytes at a level comparable with that of the BALB/c mice. The cell surface expression of endogenous class I and class II antigens on the peripheral blood lymphocytes was not affected. Analysis of these mice revealed that the expression of the class I Ld antigen significantly reduced the incidence of insulitis at 20 weeks of age. In situ hybridization of a biotinylated probe on mouse chromosomes showed that the Ld transgene was located in the E area of chromosome 6 with which no genetic linkage to insulin-dependent diabetes mellitus was demonstrated. These results suggest that the NOD-type class I molecules are involved in the development of insulitis in NOD mice.
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PMID:Prevention of autoimmune insulitis in nonobese diabetic mice by expression of major histocompatibility complex class I Ld molecules. 140 62

There is a polygenic component to rheumatoid arthritis (RA) in addition to the known association with HLA-DR4. It has previously been shown in another autoimmune disease (type I diabetes mellitus) that a gene on chromosome 11p can act with HLA-DR4 to enhance susceptibility (relative risk 5-6). It is therefore possible that this locus may also affect the development of RA. Genotype frequencies at this locus, defined by a dimorphic Fok 1 restriction site, were compared in 139 healthy controls and 213 patients with classical/definite RA. In contrast with diabetes there was no increase in genotypes lacking the Fok 1 site, either in the rheumatoid group overall (125/211 compared with 86/139 controls) or in the DR4 positive rheumatoid group (76/140 compared with controls). These results indicate that the interaction between DR4 and a locus on chromosome 11p is not common to all DR4 associated autoimmune diseases.
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PMID:Does the locus on chromosome 11 implicated in susceptibility to HLA-DR4 dependent type I diabetes mellitus also affect susceptibility to rheumatoid arthritis? 146 4

The demonstration that functionally different T-cell subsets can be defined by the isoforms of the leukocyte-common antigen, CD45, that they express, has prompted studies on the roles of these subsets in autoimmunity. The results have led to the identification of a particular subset of CD4+ T cells that have the ability to inhibit autoimmune disease. Further, it has been shown that diabetes in the B-B rat can be transferred by in vitro activation of T cells by Staphylococcal enterotoxin suggesting that superantigens may play a role in the pathogenesis of this disease. However, in this system too, it appears that a subset of T cells can inhibit the induction of autoaggressive cells. In other experimental autoimmune diseases there is evidence that CD8+ T cells can be protective and that these cells may mediate this protection by the synthesis of transforming growth factor-beta.
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PMID:T-cell subsets in autoimmunity. 146 96

It is now generally accepted that many cytokines are involved in the pathogenesis of autoimmune disease, either directly by causing tissue destruction or indirectly through the activation of autoreactive and inflammatory cells. Thus, cytokines, such as tumor necrosis factor-alpha, are implicated in the pathogenesis of rheumatoid arthritis based on in vitro studies on synovial tissue from patients with rheumatoid arthritis, which suggest that the effects of tumor necrosis factor-alpha are amplified by its potential to induce other pro-inflammatory cytokines, such as interleukin-1 and granulocyte-macrophage colony-stimulating factor. Transgenic mouse technology has shown that mice expressing the human tumor necrosis factor-alpha gene develop a polyarthritis. Interleukin-2 has also been identified by transgenic technology as a cytokine involved in the pathogenesis of insulin-dependent diabetes mellitus through the activation and stimulation of growth of autoreactive T cells.
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PMID:Cytokines in autoimmunity. 146 99

Insulin antibodies (IAA) can be detected in the serum of the majority of newly diagnosed IDDM patients prior to insulin therapy. In first degree relatives of IDDM patients, IAA are associated with an increased risk of development of IDDM. However, the disease specificity of IAA, detected by radiobinding assays, has not been addressed. We thus tested sera from patients with autoimmune disease for IAA. One of 29 (3%) patients with Graves' disease and five of 27 (19%) patients with SLE had IAA levels exceeding the range for normal controls. IAA were not detected in sera from 29 patients with Addison's disease, 15 patients with pernicious anaemia or 10 patients with increased gamma globulins. Non-specific binding of 125I-labelled insulin was increased in serum from 14 (21%) samples from patients with Graves' disease, 10 (37%) patients with SLE, one (3.2%) of 29 patients with Addison's disease and two (13%) of 15 patients with pernicious anaemia. The increased non-specific binding most likely relates to immunoglobulin binding as it was also found in eight of 10 patients with oligoclonal or polyclonal increase in gamma globulins. Our findings suggest that moderate elevations of IAA are not uncommon in patients with SLE, in whom increased non-specific binding of insulin is also common. This observation is of importance in preclinical diabetes screening studies.
Diabetes Res Clin Pract 1992 Nov
PMID:Insulin autoantibodies in patients with autoimmune diseases. 147 50

An increasing bulk of evidence suggests that type 1 (insulin-dependent) diabetes mellitus is an autoimmune disease with a strong immunogenetic background. 1st-degree relatives of type 1 diabetic patients, especially HLA-identical individuals, bear an increased risk to develop the disease. The autoimmune reactions are pronounced at the onset of disease where an infiltration of islets with T and B lymphocytes, plasma cells and macrophages can be observed. Autoreactive T lymphocytes play a crucial role among effector mechanisms which finally lead to a selective destruction of pancreatic beta cells. Disease-specific autoantibodies (Ab) include cytoplasmic islet cell Ab (ICA), islet cell surface Ab (ICSA), Ab to the 64KD islet cell protein and Ab to insulin (IAA). As ICA can be detected months or years before the onset of clinical disease, testing of individuals at risk or population screening programs can help to recognize subclinical insulitis. High titers of ICA and high levels of IAA, as measured by radioimmunoassay, indicate a high risk for progression to type 1 diabetes. A blunted first phase insulin response in the i.v. glucose tolerance test is the most sensitive sign of an irreversible metabolic deterioration. It is likely that immunotherapy at a prediabetic state will be more efficacious than its initiation after the clinical manifestation of diabetes. However, the appropriate immunotherapeutical strategies are yet to be worked out.
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PMID:Etiology and pathogenesis of type 1 diabetes. 149 Jun 74


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