Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004364 (autoimmune disease)
 24,845 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Insulin autoantibodies in patients with autoimmune diseases. 147 50

Current theories of the aetiology of RA point to a central role for the trimolecular complex comprising the MHC class II molecule on the surface of the APC, the antigenic peptide and the TCR on the disease-inducing T cell. Thus the arthritogenic T cell is an important target for new therapy. However, it cannot be directly identified because the causative antigen is unknown, so indirect techniques such as TCV and TCR peptide vaccination are required. In TCV, T cells thought to mediate the disease, in an activated and attenuated form, are injected into the patient, who then develops a specific immune response against these pathogenic T cells. TCV has been shown to be effective in protecting against and treating a variety of animal models of autoimmune disease, including AA, EAE and IDDM in NOD mice. The vaccines initially comprised clones and lines of T cells shown to be capable of transferring the disease, but later unseparated LN cells were also shown to be effective, paralleling more closely the human situation. Interestingly, it has become clear that TCV does not create its own regulatory network but amplifies a natural immunoregulatory network which forms as the disease develops. The major stimulating moiety on the vaccinating T cell is its receptor (anti-idiotypic response), although there is also an anti-ergotypic (anti-activated T cell) response. For this reason the technique of TCR peptide vaccination was developed, which utilizes only a short peptide from the TCR of the disease-causing cells to stimulate an immune response against them. This is effective in the prevention and treatment of EAE, where there is a preferential usage of TCR-V beta 8 by encephalitogenic T cells. The application of both these techniques to human autoimmune disease is in its infancy. Studies of TCV in MS and RA have not shown clear-cut clinical benefit, although immunological changes have been observed; comparison of methodology with the animal work and assessment of results are complex and further studies are in progress. Studies of TCR peptide vaccination in MS and RA are handicapped by the lack of a consensus on TCR usage in these conditions, but a limited study is underway in MS.
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PMID:Management of early inflammatory arthritis. Intervention with immunomodulatory agents: T cell vaccination. 152 47

Effective fuel metabolism is dependent on balances among exogenous and endogenous fuel availability, the glucagon/insulin ratio, and tissue insulin sensitivity. Diabetes mellitus results when imbalances occur. The resultant metabolic derangement is accompanied by abnormalities in carbohydrate, protein, and fat metabolism. The two most common forms of diabetes are insulin dependent (IDDM) and noninsulin dependent (NIDDM). IDDM is an autoimmune disease, characterized by insulinopenia and ketosis. NIDDM is related to impaired insulin secretion, defective tissue sensitivity, and abnormalities in glucose transporter proteins. This article describes normal fuel metabolism and traces the abnormal metabolic processes that lead to both IDDM and NIDDM.
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PMID:Normal fuel metabolism and alterations in diabetes mellitus. 184 Sep 66

It is well established that insulin-dependent diabetes (IDDM) is an autoimmune disease with a strong genetic link to the HLA locus. It is less well understood, however, how the destruction of the insulin-producing beta cells is effected and why neighboring non-beta islet cells are spared. Also incompletely explained are the observations that, unlike other autoimmune diseases such as multiple sclerosis, IDDM does not preferentially affect females, the incidence of the disease is highest among young adults, and there are temporal correlations between the onset of the disease and emotional trauma. We have addressed some of these questions by using transgenic mice that constitutively express the MHC class I antigen Dd in the beta cells of the pancreas. Although both male and female Ins.Dd mice expressed equivalent amounts of the Dd protein only the males developed diabetes. The diabetes in the males could be reversed by castration, and the normoglycemic females became diabetic following either ovariectomy and the implantation of a slow-release pellet containing testosterone or the inclusion of dexamethasone in the drinking water. In contrast, transgenic mice that expressed the herpes simplex virus type 1 glycoprotein D in the pancreatic beta cells were normoglycemic and showed no obvious histopathological consequences. The observation that the beta-cell dysfunction by the increased expression of the MHC class I protein Dd cannot be induced by the herpes viral protein suggests that the cellular damage is related to a specific structure or function of the MHC proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Male-specific beta-cell dysfunction and diabetes resulting from increased expression of a syngeneic MHC class I protein in the pancreata of transgenic mice. 196 48

IgA nephropathy (IgAN) has been associated with HLA-DR4. We have recently described two non-allelic Taq I DQ beta gene-associated fragments sized 2.0 kb (T2) and 6.0 kb (T6), which strongly associate with DR4. T2 represents a polymorphism of the DQ beta gene and has been redesignated DQw8 (10th International HLA Workshop). The origin of the T6 fragment has not been determined, but probably represents a polymorphism of either the DQ beta or DX beta gene. When present together T2 and T6 define a subgroup of DR4 subjects at high risk of developing autoimmune disease. We have, therefore, studied DQ beta gene polymorphisms in IgAN. The DR antigen distribution was similar in IgAN and normal controls. The T2+/T6+ phenotype was present in 49% patients with IgAN compared to 15% of controls [P less than 0.0001, chi 2 = 32.8, Cramer's V = 0.41; relative risk = 5.5 (range, 2.8-11.0)]. Seventy-two percent of DR4+ IgAN patients and 29% of DR4+ controls were T2+/T6+ (P = 0.007, chi 2 = 17.0). These findings confirm the hypothesis that disease susceptibility genes are important in IgAN, and suggest that the putative gene(s) are located within or near to the DQ subregion. Moreover, similar DQ beta gene associations have been found in IDDM and pemphigus vulgaris, pointing to a common immunogenetic mechanism predisposing to several autoimmune diseases.
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PMID:HLA DQ region gene polymorphism associated with primary IgA nephropathy. 196 92

We studied the association of a T-cell receptor (TcR) beta restriction fragment length polymorphism (RFLP) and a new TcR-alpha RFLP with insulin-dependent (Type I) diabetes mellitus. This study is part of our effort to find new non-HLA disease genes involved in this chronic organ-specific autoimmune disease. Distribution of a 9.2 kb and a 10.0 kb diallelic TcR beta 2 RFLP was not different in diabetics and controls. A new TcR-alpha RFLP, which gave a 2.7 kb Hind III restriction fragment (A2 allele) was found with a frequency of 0.78 in a population of 78 IDDM patients, compared to 0.68 in 68 control subjects (X2 = 3.62, p = 0.057). In 11 multiplex families studied, a high prevalence of the A2 allele was also observed, but cosegregation with the disease was not seen. Our data suggest that a TcR beta 2 RFLP is not associated with the disease, whereas a particular T-cell receptor alpha germline RFLP (A2 allele) is increased in Type I diabetics although formal proof of linkage is lacking. HLA typing reconfirmed that the HLA-DR4 specificity and the DQ allele HLA-DQw8 are primary risk markers in insulin-dependent (Type I) diabetes mellitus.
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PMID:TcR-alpha and TcR-beta dialellic RFLPs in insulin-dependent (type I) Caucasian diabetic patients. 198 28

It has now become clear that certain HLA antigens are associated with disease susceptibility more than any other genetic markers. Insulin-dependent diabetes mellitus (IDDM or type I) is an HLA-associated condition. Moreover, there is evidence to show that IDDM is a genetically programmed autoimmune disease. Studies of the HLA-DR region have shown a strong association with IDDM, with over 90 per cent of IDDM patients possessing DR3 and/or DR4. Although the HLA-DR region is a major component in the inherited disease susceptibility, it is not the only gene region involved. Recent studies demonstrated that HLA-DQ may be more closely linked to the disease locus than HLA-DR. Sequence analysis of the HLA-DQ3 gene products suggest that a single amino acid (aspartic acid) at position 57 is uniquely important for determining susceptibility or resistance to IDDM. Although there is a strong association of certain HLA loci with IDDM, it may not explain nor account for all the genetic susceptibility to the disease. It seems that 60 per cent of the genetic basis of IDDM is related to the HLA gene (chromosome 6) and another 40 per cent is non-HLA-associated (i.e., chromosomes 2, 7, 11, and 14). Even though great progress has been made in the understanding of the genetics of IDDM, the mode of inheritance of the disease remains controversial. The present review discusses various aspects of the autoimmune process believed to be involved in pancreatic beta cell destruction in individuals genetically susceptible to IDDM. The possible modes of inheritance and new data regarding estimated risks of transmitting the disease are presented.
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PMID:Insulin-dependent diabetes mellitus and immunogenetics: maternal and fetal considerations. 205 68

Insulin dependent diabetes mellitus is an autoimmune disease with HLA-related genetic susceptibility. There is a latent phase before overt disease. During this phase islet cell antibodies (ICA) as a marker of humoral autoimmunity are detected and i.v. glucose tolerance test (IVGTT) is decreased. The aim of our work was to correlate IVGTT, HLA typing and ICA testing in all siblings of IDDM patients in order to identify high risk subjects (HRS). IVGTT showed significantly lower insulin levels in siblings vs controls (P less than 0.0001). This phenomenon could be caused by HLA unrelated genetic predisposition to low insulin secretion. Insulin level values of ICA+ siblings were lower than those of ICA- siblings, even if the difference was not significant.
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PMID:[Immunogenetic and functional study of first-degree relatives of patients with type I diabetes mellitus for identifying prediabetic subjects]. 213 76

Insulin autoantibodies (IAA) are well documented in patients with insulin-dependent diabetes (IDDM) prior to the administration of insulin and in patients with reactive hypoglycaemia--the insulin autoimmune syndrome (IAS). It has been suggested that IAA can be induced by the administration of drugs containing sulphydryl groups, such as carbimazole, and they have been frequently described in Graves' disease. An alternative explanation is the clustering of autoantibodies in autoimmune disease. We studied 39 patients (37 females, two males, age range 14 to 61 years; mean 33.8 years) with proven Graves' disease and no previous treatment with carbimazole. Fifteen of the 39 patients had a family history of other autoimmune diseases. IAA and thyroid autoantibodies were assayed at diagnosis and monthly thereafter while on treatment with carbimazole, for up to 6 months. IAA were measured using a direct-binding solid-phase ELISA and specificity was confirmed by absorption studies using insulin covalently coupled to Sepharose beads. At diagnosis 33 of the 39 patients (85%) were positive for thyroid microsomal antibodies, 13 (33%) were positive for thyroglobulin antibodies, and 4 (10%) were positive for IAA. All IAA-positive patients had microsomal antibodies at diagnosis, and two had thyroglobulin antibodies in addition. After 4 months on carbimazole, the frequency of thyroid microsomal autoantibodies was unchanged (83%), while that of anti-thyroglobulin antibodies had fallen (8.6%). All four IAA-positive patients remained positive, and studies of binding to human, porcine and bovine insulin demonstrated that one serum, initially human insulin specific, later became cross-reactive with all three. We conclude that low titres of IAA are found in Graves' disease, and are associated with the presence of autoimmunity rather than the carbimazole. Symptomatic hypoglycaemia, however, is rare in Caucasian patients.
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PMID:Insulin autoantibodies in Graves' disease--before and after carbimazole therapy. 234 Jul 91

Insulin-dependent diabetes mellitus (IDDM, type I) is an autoimmune disorder exhibiting a strong association with particular haplotypes of the major histocompatibility complex (MHC). We have previously shown that the u haplotype of the rat MHC (RT1) is absolutely required for expression of IDDM in the BB rat model of the disease. To define the precise regions of the RT1 contributing to disease occurrence and to address the mechanism by which the associated haplotype participates in disease pathogenesis, we have transferred recombinant haplotypes bearing the IDDM-associated MHC in defined regions onto the BB rat genetic background. In this report, we present data from two breeding studies utilizing the r8 haplotype (RT1AaBuDuEuCu) that demonstrate that (1) the RT1A locus is not involved in the disease association, (2) the MHC genes determining disease susceptibility are not unique to the BB rat, and (3) IDDM resistance genes are found outside the MHC. We also present evidence that the immunoregulatory defect characteristic of BB rats enhances the incidence of IDDM although it is not absolutely required for disease expression. We were able to track the transmission of the recombinant haplotypes in diabetic progeny using a combination of monospecific alloantisera and restriction fragment length polymorphism analysis using locus-specific MHC gene probes.
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PMID:Susceptibility and resistance genes to insulin-dependent diabetes mellitus in the BB rat. 251 27


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