Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nonobese diabetic (NOD) mouse, in which major histocompatibility complex genes may be involved in the susceptibility to diabetes, has been developed as a model of autoimmune diabetes. The NOD mouse expresses I-A-encoded class II major histocompatibility complex antigens, which differ from those of other mouse haplotypes by the presence of a serine at position 57 of the A beta chain. Identifying islet autoantigens may help elucidate the role of class II antigens in the activation of autoreactive T cells and, thus, in the development of diabetes. We have detected autoantibodies directed against a 58-kDa islet cell antigen in NOD mice but not in other strains, including lupus-prone mice. Apart from insulin-secreting cells, the 58-kDa antigen was only found to be expressed by neuroblastoma cells and was identified as peripherin, an intermediate filament protein previously characterized in well-defined neuronal populations. This autoantigen cross-reacted with I-Anod class II antigens, suggesting that it may contribute to defective self-tolerance of islet beta cells in the NOD mouse.
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PMID:Peripherin: an islet antigen that is cross-reactive with nonobese diabetic mouse class II gene products. 172 86

Only a few immunosuppressive drugs can be used today. These are: corticosteroids, azathioprine, cyclophosphamide, ciclosporine A, accessorily chlorambucil and methotrexate. They all have different actions on immune responses. The use of these drugs has completely changed the prognosis of autoimmune diseases such as systematic lupus erythematous, polyartheritis nodosa, Wegener's granulomatosis. Nevertheless treatment of other autoimmune diseases, such as type I insulin-dependent diabetes mellitus or multiple sclerosis, has been inconclusive.
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PMID:[Immunosuppressive drugs and autoimmune diseases]. 175 27

Class II major histocompatibility complex molecules are critical in both normal and abnormal immune responses. Both in mice and in humans, these molecules have been implicated in the development of various diseases, including insulin-dependent diabetes mellitus and systemic lupus erythematosus. The MRL/lpr mouse strain spontaneously develops a lupus-like illness with features that include anti-DNA antibodies, glomerulonephritis, and early death. We evaluated the structure of class II molecules from these mice, to investigate for unique sequences that might contribute to autoimmunity. Utilizing the polymerase chain reaction, we sequenced the second exons from the I-A and I-E genes of MRL/lpr and MRL-+/+ mice. We found that at the nucleotide level, there are several changes between MRL class II genes and the previously sequenced "k" haplotype, but at the protein level, they are identical. Furthermore, by comparing the sequences of class II genes from several strains of autoimmune mice, we found that there are conserved amino acids in the third hypervariable region of the I-E beta chain which may be important in the development of autoimmunity.
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PMID:Sequence of class II major histocompatibility complex genes from MRL mice. Conserved amino acids in the I-E beta chains from autoimmune mice. 195 19

Several studies have demonstrated abnormalities of T cell regulation of Epstein-Barr virus-induced B cell activation in systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, and systemic sclerosis. However, a normal suppressive peripheral T cell function was observed in Graves' disease. To investigate whether this abnormality is a common feature to other autoimmune diseases, we studied T cell regulation of Epstein-Barr virus induced B cell activation in 15 newly diagnosed type 1 (insulin dependent) diabetes mellitus patients and 10 normal control subjects. Peripheral B lymphocytes infected with Epstein-Barr virus were cultured for 20 days in the presence or absence of autologous T cells at different ratios (1:1 and 1:4). IgM and IgG secretions into the supernatants were determined using an enzyme-linked immunosorbent assay. The extent of suppression when T cells were added, as measured by a suppression ratio, was not significantly different in type 1 (insulin dependent) diabetes mellitus patients and normal subjects. We conclude that in type 1 (insulin dependent) diabetes mellitus, the autoimmune reactivity is not dependent upon a generalized suppression defect. It can be hypothesized, therefore, that in type 1 diabetes mellitus as well as in Graves' disease, a local or organ specific suppressor deficit may induce the autoimmune phenomena.
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PMID:Normal suppressive T cell function of Epstein-Barr virus induced B cell activation in type 1 (insulin dependent) diabetes mellitus. 196 82

Insulin- and anti-immunoglobulin-antibodies have been recently reported in pre-diabetic subjects: the former has been proposed as a predictive marker of Type I diabetes in non-diabetic-subjects. To evaluate the diabetes-related specificity of these antibodies, the presence of insulin autoantibodies, using a recently developed and highly sensitive competitive radioimmune assay, and of anti-immunoglobulin antibodies together with that of immune complexes and of other autoantibodies has been investigated in patients with organ- or non-organ-specific autoimmune diseases. One hundred and eleven serum samples were assayed from patients with Graves' disease, primary hypothyroidism, chronic autoimmune thyroiditis, Addison's disease, chronic autoimmune hepatitis, pernicious anemia, lupus erythematosus, and rheumatoid arthritis, together with 45 serum samples from normal subjects. From patients with autoimmune diseases, 32.4% of all sera revealed values of insulin autoantibodies above the limit of positivity (p less than 0.001); anti-immunoglobulin antibodies were present in 4.1% of patients (NS); immune complexes were found in 19.5% (NS) of all patients, but in 38% of patients with Graves' disease and chronic hepatitis (p less than 0.02). There was a trend for multiple autoantibody positivity to be associated with high levels of insulin autoantibodies (p less than 0.05). Thus, whereas contrary to expectation anti-immunoglobulin antibodies are not associated with non-diabetes-related autoimmune diseases, increased humoral immunoresponsiveness to endogenous insulin appears to be related to autoimmunity in general rather than restricted to Type I diabetes.
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PMID:Autoantibodies to insulin do appear in non-diabetic patients with autoimmune disorders: comparison with anti-immunoglobulin antibodies and other autoimmune phenomena. 218 33

Molecular and genetic tools have been used to shed light on the genes that contribute to susceptibility to murine lupus and the mechanisms that lead to immunopathology. The MHC genes and their products have been consistently shown to contribute toward the development of disease. To understand the contribution of MHC-class II genes, our laboratory had derived two inbred strains of mice, NZB.H-2bm12 and NZB.H-2b. These new colonies of mice were studied and compared in the 10th generation backcross; inbreeding was serially followed by H-2 typing, responses to beef/porcine insulin, and the presence of the B6 Ig allotype, IgG2ab. Of great interest is the finding that NZB.H-2bm12, in contrast to NZB.H-2b or NZB (H-2d), mice develop high titer autoantibodies to dsDNA. This result is unique because NZB (H-2d) mice, unliked NZB x NZW (NZB/W F1) or NZB x SWR (SNF1) hybrids do not develop autoantibodies to dsDNA, even after immunization. NZB mice, in contrast, are characterized only by autoantibodies to ssDNA. Our observation is also striking because the gene conversion that resulted in the I-A beta bm12 mutation occurred at amino acid residues 68, 71, and 72 of I-E beta b. Recently the contribution of NZW to accelerated autoimmunity in the NZB x NZW F1 hybrid has also been linked to H-2 and a single amino acid change at amino acid 72 of I-E beta. Thus, amino acid residue 72 may be a hot spot for disorders of immune regulation when superimposed on the appropriate genetic background. NZB mice expressing the I-Abm12 mutation will allow specific dissection of the requirements for autoantibody production to dsDNA uncomplicated by heterozygosity.
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PMID:The BM12 mutation and autoantibodies to dsDNA in NZB.H-2bm12 mice. 235 82

The NOD mouse is a model of human juvenile type I diabetes mellitus. As in humans and in the BB rat model, the development of diabetes in NOD mice is accompanied by evident manifestations of cell-mediated and humoral autoimmunity. Beside autoantibodies directed at putative islet cell antigens, NOD sera contain antibodies with specificity for lymphocyte cell-surface determinants. Here we demonstrate that these anti-lymphocyte antibodies have the same characteristics of target cell specificity, of isotype, and of temperature reactivity, as do natural thymocytotoxic autoantibodies (NTA) from lupic NZB mice, or from mice undergoing polyclonal B cell activation. We also demonstrate that the thymocytotoxic activity of NOD sera is not due to cross-reactive anti-insulin antibodies. Biochemical characterization of the determinants recognized by these anti-lymphocyte antibodies reveals two membrane-associated proteins of 28 and 33 kD, partially similar to the two peptides recognized by NTA from NZB mice (30 and 33 kD). Altogether, these results suggest that NOD mice develop manifestations of polyclonal B cell activation similar to those observed in lupus-prone mice. The relationship of these anomalies with the organ-specific pancreatic disease remains to be properly evaluated.
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PMID:Natural thymocytotoxic autoantibodies in non-obese diabetic (NOD) mice: characterization and fine specificity. 239 10

A 47-year-old man with Graves' disease suffered from a feeling of hunger and sweating in the night, polyarthralgia and fever one month after the start of treatment with methimazole. The above symptoms were ascribed to the side effects of methimazole; insulin autoimmune syndrome and lupus-like syndrome. The change in the antithyroid drug to propylthiouracil caused an amelioration of the symptoms. In addition to an anti-insulin antibody with a high binding capacity, hyperglucagonemia (260 pg/ml with a plasma glucose level of 61 mg/dl) was observed, which returned to normal in parallel with the decrease in the insulin binding capacity of the plasma one month after beginning the treatment with propylthiouracil. A normal decrease in the plasma glucagon level due to exogenous insulin (2 mU/kg/min) was observed with the euglycemic clamp. However, the plasma glucagon level was not suppressed by the oral glucose loading and elicited a poor response to the arginine infusion. Taking previous reports into account, this basal hyperglucagonemia seems to be a characteristic finding in the insulin autoimmune syndrome, while a sluggish response of glucagon to oral glucose or arginine infusion might be ascribed to hyperthyroidism. This is the first case report concerning a kinetical study of the glucagon secretion in insulin autoimmune syndrome with Graves' disease.
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PMID:Hyperglucagonemia of insulin autoimmune syndrome induced by methimazole in a patient with Graves' disease. 265 8

During a survey period of 28 years a total of 449 patients suffering respectively from pemphigus, systemic lupus erythematous and chronic nephritis was admitted to the hospital. Of the 286 patients who received glucocorticoid treatment 28 were found to have steroid diabetes (9.8%). The incidences of steroid diabetes in these diseases were as follows: pemphigus 20% (7/35), systemic lupus erythematous 12.5% (14/112), chronic nephritis 5% (7/139). Two thirds of the diabetic subjects appeared asymptomatic, while the remainder showed polydipsia and polyuria. Renal glucosuria was seen in 3 cases and hyperosmolar hyperglycemia in 4. Blood glucose level in 10 out of the 21 remaining cases was 8.9 +/- 1.5 mmol/L and in the other 11 cases 14.8 +/- 2.4 mmol/L. Generally, the treatment of steroid diabetes is not intricate. Satisfactory improvement was seen in about 80% of the patients if a strict line of therapy against primary diabetes was oriented. In this series 18 patients did well under the treatment either with reduction of steroid or with use of oral hypoglycemic agents or insulin or both. Their blood glucose levels returned to normal and urine sugar disappeared rapidly. Four of the 5 deaths were caused by their primary diseases. One died of pemphigus complicated with infection and shock exhibiting an ante mortem blood glucose level as high as 31.7 mmol/L, obviously hyperosmolar status being the predisposing factor. Due to the fact that most of the steroid diabetic patients were clinically asymptomatic, delayed or misbranded diagnosis was not infrequently seen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Steroid diabetes: an analysis of 28 cases]. 280 46

This report describes a new method for detecting and quantitating those immunoglobulins G (IgG) in serum that are related to Graves' disease. The method is based on previous observations which indicate that the guinea pig fat cell membrane (FCM) is capable of binding Graves'-specific IgG, but does not bind the IgG common to Graves' disease and Hashimoto's disease, such as antimicrosomal antibodies. Crude FCM preparations were iodinated by a lactoperoxidase technique and were then treated with Triton X-100 to yield a solubilized radioiodinated FCM (SFCM) preparation. SFCM, which retained bovine (b) TSH binding and Graves'-IgG binding properties, provided a radioactively labeled receptor with which to test for the presence of fat cell-binding IgG (FBI) in immunoprecipitates prepared by reacting these IgG with antibody against the Fc fragment of human IgG. FBI values (percentage of added SFCM bound to immunoprecipitate; mean + SD) in IgG from 16 patients with thyrotoxicosis caused by Graves' disease (6.0 +/- 1.7) were completely separated from those in IgG from 16 normal subjects (0.4 +/- 0.3). IgG from 2 hypothyroid patients with Hashimoto's disease, which were strongly positive in the TSH binding inhibition (TBI) assay, yielded FBI values within the range in Graves' disease, but values in TBI-negative IgG from 15 other patients with Hashimoto's disease were normal (0.0 +/- 0.9). Moderately false positive FBI values were found in the IgG of 15 patients with rheumatoid arthritis or systemic lupus erythematosis, all rheumatoid factor positive, 3 of which were also TBI positive. In IgG from Graves' disease and those from patients with TBI-positive collagen-vascular disease, binding of SFCM was inhibited by bTSH in a dose-dependent manner. As with binding of TSH to thyroid plasma membranes, similar but less potent inhibition of binding of IgG to SFCM was produced by LH, FSH, and hCG, but not by insulin, glucagon, PRL, or ACTH. FBI values in TBI-negative IgG from patients with collagen-vascular disease were also decreased by TSH, but higher concentrations of bTSH were required. In 40 IgG from among the various clinical groups tested, a significant correlation was found between FBI values and TBI activity (r = 0.48; P less than 0.01). In addition, among 10 IgG from Graves' disease and 6 from collagen-vascular disease patients, a very close correlation (r = 0.89; P less than 0.001) was noted between their TBI activity and the extent to which their FBI values were decreased by a standard concentration of bTSH.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Detection and measurement of fat cell-binding immunoglobulins: a new method applicable to the diagnosis and study of Graves' disease. 299 73


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