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)

Right classification of diabetes is important clinical issue. The aim of present study was to compare clinical, biochemical and immunological features, to analyze their practical use and to establish new decision tree which make the distinction between diabetes type 1, LADA, diabetes type 2 and MODY. We studied 97 not obese (mean BMI 26.3 +/- 4.9 kg/m2) patients aged 14 to 70 years, mean age 43 +/- 11.7 years, 53 women, 44 men. Mean duration of diabetes--2.3 +/- 4.3 years. We measured basal and stimulated C-peptide (6 minutes after 1 mg i.v. glucagon) (ELISA) and antibodies titers to glutamic acid decarboxylase--antiGAD65, tyrosine phosphatase-like molecule--IA2 and insulin--IAA (RIA). Autoimmune diabetes (LADA, type 1) was diagnosed with presence of one or more islet antigen antibodies. The highest frequencies had anti-GAD antibodies 33/97 (34%). The most complicated was to sort out group of patients with LADA. Comparison between this group and patients with diabetes type 2 have shown that BMI, co-existence of autoimmune disease, autoimmune markers and basal and stimulated C-peptide level measured at entry for the classification were useful in differentiation. Moreover we observed significantly lower C-peptide basal, stimulated and over basal level in group with MODY diabetes in comparison to diabetes type 2 patients. In the studied group were 5 patients with diabetes type 2 and obesity, in relatively young age. At the end there was one case of ADM (atypical diabetes mellitus). Clinical criteria for the classification of diabetes not always correlated with diagnosis. Autoimmune markers, basal and stimulated C-peptide were useful specially in differentiation between LADA and diabetes type 2 or diabetes type 1. Autoimmune diabetes co-existe with autoimmune disease. Proposed diagnostic scheme take for consideration presence of autoantibodies as well as C-peptide criteria.
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PMID:[Clinical, biochemical and immunological characteristic of diabetes type I, LADA, diabetes type II, and MODY patients]. 1268 30

Genetic vaccines are promising candidates for prevention of type 1 diabetes, an autoimmune disease resulting from cell-mediated destruction of pancreatic beta cells. It is known that the prophylactic effect and immune responses induced by administration of a genetic vaccine can depend on site of delivery. In the work presented here, we used the NOD mouse model for type 1 diabetes to evaluate different routes of delivery for DNA vaccines coding for the beta-cell antigen glutamic acid decarboxylase (GAD). Plasmid DNA coding for intracellular or secreted GAD was given via either the intramuscular (i.m.), intradermal (i.d.), or oral route, using, respectively, 300, 100, or 300 micro g DNA per mouse. Results indicated that both i.d. and oral delivery of GAD-encoding DNA were more effective than i.m. delivery for disease suppression. In addition, cytokine-specific ELISpot analysis indicated that immune responses induced by the different immunization protocols were more dependent on the cellular localization of GAD antigen than on the delivery route, while ELISA of anti-GAD serum antibody isotypes indicated that i.d. delivery of DNA was most likely to induce a Th2-like response. Our results suggest that i.d. or oral delivery of a genetic vaccine for type 1 diabetes might be preferable over the i.m. route in a future clinical setting.
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PMID:Intradermal or oral delivery of GAD-encoding genetic vaccines suppresses type 1 diabetes. 1282 99

We report a case of primary biliary cirrhosis (PBC) complicated by slowly progressive insulin-dependent diabetes mellitus (SPIDDM). A 67-year-old woman was diagnosed as having PBC based on clinical manifestations and a positive result of anti-mitochondrial antibody. Furthermore, SPIDDM was diagnosed by her clinical course and a positive result of anti-glutamic acid decarboxylase antibody. Both PBC and SPIDDM are considered to be autoimmune diseases. However, the coexistence of PBC and SPIDDM is extremely rare. Liver cirrhosis sometimes accompanies hyperglycemia. When the etiology of liver cirrhosis is an autoimmune disorder such as PBC, SPIDDM should be considered as a cause of hyperglycemia.
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PMID:A patient with primary biliary cirrhosis complicated with slowly progressive insulin-dependent diabetes mellitus. 1285 47

Recent reports describe the detection of high titres of antibodies to glutamic acid decarboxylase (GAD-Ab) in the serum and cerebrospinal fluid (CSF) of patients with cerebellar ataxia. Most of these cases are females with Polyglandular Autoimmune Disorder who develop a chronic cerebellar syndrome. The CSF profile is in keeping with an autoimmune disorder and intrathecal GAD-Ab synthesis has been demonstrated. The ataxia could reverse after immunomodulatory treatments suggesting a possible pathogenetic role for GAD-Ab.
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PMID:Cerebellar ataxia associated with anti-glutamic acid decarboxylase autoantibodies. 1288 38

Stiff person syndrome (SPS) is a chronic autoimmune disease associated with humoral and cellular immune responses to glutamic acid decarboxylase (GAD) 65. Another chronic autoimmune disease, type 1 diabetes (T1D), is also associated with autoimmune responses to this antigen, but T1D patients develop SPS only extremely rarely and only a third of SPS patients develop T1D (mostly mild manifestations in adulthood). In a previous study, we described important differences between T1D and SPS in the autoimmune response to GAD 65: (1) T cells of SPS patients recognize epitopes in the middle of GAD 65 (amino residues 81-171 and 313-403), whereas patients with T1D preferentially recognize another middle (161-243) and a C-terminal region (473-555); and (2) GAD antibodies (Abs) were nearly exclusively of the Th1-associated IgG1 type in T1D, whereas SPS patients had both Th1- and Th2-associated IgG4 and IgE GAD Abs. These differences were not simply related to different HLA alleles. Fine epitope mapping revealed further distinct T cell epitopes in both diseases despite similar HLA background. Therefore, a single autoantigen can elicit different immune responses causing distinct chronic autoimmune diseases possibly related to a Th1 or Th2 bias of the disease.
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PMID:Humoral and cellular autoimmune responses in stiff person syndrome. 1459 79

IL-18 is now identified as a pleiotropic cytokine that acts as a cofactor for both Th1 and Th2 cell development. Type 1 diabetes is considered a Th1-type autoimmune disease, and to date, the suppressive effect of exogenous IL-18 on the development of diabetes has been reported in 10-wk-old nonobese diabetic (NOD) mice. In the present study we administered exogenous IL-18 systemically in 4-wk-old NOD mice using i.m. injection of the IL-18 expression plasmid DNA (pCAGGS-IL-18) with electroporation. Contrary to previous reports, the incidence of diabetes development was significantly increased in NOD mice injected with pCAGGS-IL-18 compared with that in control mice. Systemic and pancreatic cytokine profiles deviated to a Th1-dominant state, and the the frequency of glutamic acid decarboxylase-reactive IFN-gamma-producing CD4(+) cells was also high in the IL-18 group. Moreover, it was suggested that the promoting effect of IL-18 might be associated with increased peripheral IL-12, CD86, and pancreatic IFN-inducible protein-10 mRNA expression levels. In conclusion, we demonstrate here that IL-18 plays a promoting role as an enhancer of Th1-type immune responses in diabetes development early in the spontaneous disease process, which may contribute to elucidating the pathogenesis of type 1 diabetes.
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PMID:Systemic administration of IL-18 promotes diabetes development in young nonobese diabetic mice. 1463 96

DNA vaccination with antigen expression plasmids has been introduced as a simple method of inducing immunity to the antigens of infectious agents or tumors. Although DNA vaccination is generally immunostimulatory, it is possible to design suppressive vaccines that protect against autoimmune diseases such as Type 1 diabetes. In mice prone to diabetes, investigators have delivered a plasmid encoding an islet-cell antigen such as insulin B chain, glutamic acid decarboxylase, or antigen/immunoglobulin G-Fc fusion constructs, with or without co-delivery of another gene encoding a cytokine or other immunoregulatory molecule. This approach has led to protection against disease, related to the generation of regulatory T-cells and increased production of regulatory cytokines. DNA vaccination is a promising approach to autoimmune disease prevention.
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PMID:Prevention of autoimmune diabetes by DNA vaccination. 1471 37

The structurally related group II pyridoxal phosphate (PLP)-dependent amino acid decarboxylases glutamic acid decarboxylase (GAD), aromatic L-amino acid decarboxylase (AADC), and histidine decarboxylase (HDC) are known autoantigens in endocrine disorders. We report, for the first time, the prevalence of serum autoantibody reactivity against cysteine sulfinic acid decarboxylase (CSAD), an enzyme that shares 50% amino acid identity with the 65- and 67-kDa isoforms of GAD (GAD-65 and GAD-67), in endocrine autoimmune disease. Three of 83 patients (3.6%) with autoimmune polyendocrine syndrome type 1 (APS1) were anti-CSAD positive in a radioimmunoprecipitation assay. Anti-CSAD antibodies cross-reacted with GAD-65, and the anti-CSAD-positive sera were also reactive with AADC and HDC. The low frequency of anti-CSAD reactivity is in striking contrast to the prevalence of antibodies against GAD-65, AADC, and HDC in APS1 patients, suggesting that different mechanisms control the immunological tolerance toward CSAD and the other group II decarboxylases. Moreover, CSAD may be a useful mold for the construction of recombinant chimerical antigens in attempts to map conformational epitopes on other group II PLP-dependent amino acid decarboxylases.
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PMID:Analysis of antibody reactivity against cysteine sulfinic acid decarboxylase, a pyridoxal phosphate-dependent enzyme, in endocrine autoimmune disease. 1507 Sep 23

Type 1 diabetes is an autoimmune disease with an inflammatory process directed against the beta cells in pancreas. This investigation aimed at studying the immune response during the first 3 months after the diagnosis of type 1 diabetes, with focus on the balance of T-helper 1 (Th1)- and Th2-like cytokines, produced spontaneously and in response to relevant autoantigens. Peripheral blood mononuclear cells (PBMCs) were collected from type 1 diabetic children (10-17 years) at 5, 20, 35 and 90 days after diagnosis. Expression of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) mRNA were detected by real-time reverse transcriptase polymerase chain reaction and IFN-gamma, IL-10 and IL-13 by enzyme-linked immunosorbent assay in cell supernatant after stimulation with a glutamic acid decarboxylase 65 (GAD(65))-peptide [amino acid (a.a.) 247-279], insulin, the ABBOS-peptide (a.a. 152-169), phytohaemagglutinin and keyhole limpet haemocyanin. Spontaneous and antigen-induced expression and secretion of cytokines were low at the diagnosis of type 1 diabetes. During the first month, after diagnosis, the GAD(65)-peptide caused an increased ratio of IFN-gamma/IL-4 mRNA expression (P < 0.05) and increased secretion of IFN-gamma (P = 0.07). Expression of IFN-gamma mRNA did also increase from stimulation with insulin (P < 0.05), even though cytokine secretion remained low. Thus, duration after diagnosis as well as metabolic state should be carefully considered both in studies of the pathogenesis of type 1 diabetes and in immune intervention studies at onset.
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PMID:Cytokine profile in children during the first 3 months after the diagnosis of type 1 diabetes. 1514 63

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease in which insulin-producing beta cells of the pancreatic islets of Langerhans are destroyed. The nonobese diabetic (NOD) mouse is one of the rare spontaneous models that enable the study of prediabetic pancreatic events. The etiology of the autoimmune attack in human and animal T1D is still unknown, but genetic and environmental factors are involved in both cases. Although several autoantigens have been identified and defective immune-system regulation is implicated, this information does not satisfactorily explain the generally accepted beta-cell specificity of the disease or how so many and diverse environmental factors intervene in its pathogenesis. Based on data obtained from evaluating glucose homeostasis in a variety of situations, particularly stress and cytokine administration, in young prediabetic NOD mice, the author hypothesizes that the islet of Langerhans is a major actor, and its altered regulation through environmentally induced insulin resistance might reveal latent T1D. It is also postulated that T1D pathogenesis might be linked to abnormal pancreas development, probably due to disturbances of glutamic acid decarboxylase (GAD)+ innervation phagocytosis by defective macrophages during the early postnatal period. Also discussed is the role of defective presentation of pancreatic hormones and GAD in the thymus, and its potential repercussion on T-cell tolerance. Observations have demonstrated that the diabetogenic process in the NOD mouse is extremely complex, involving neuroendocrine immune interaction from fetal life onward.
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PMID:Neuroendocrine immuno-ontogeny of the pathogenesis of autoimmune disease in the nonobese diabetic (NOD) mouse. 1522 72


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