Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Forty-one simplex and 6 multiplex families of Brazilian IDDM patients were studied by the indirect immunofluorescence technique to determine the prevalence of the following autoantibodies: islet cells (ICA), islet cells which fix complement (ICA-CF), thyroid microsomes (TMA), thyroglobulin (TGA), and gastric-parietal cells (PCA). A total of 54 IDDM patients belonging to two family groups were analyzed. 2. A significantly higher frequency of ICA-CF and TMA was detected among the siblings from multiplex families than among those from simplex families (18.7% vs 1.7%). 3. A prospective study of 5 ICA-positive siblings was undertaken, and 2 who later became diabetic were found to be positive to both ICA and ICA-CF. 4. The prevalence of islet-cell antibodies in these 54 Brazilian IDDM patients and their unaffected first-degree relatives from genetically mixed groups suggests that the humoral autoimmune mechanisms of the disease are probably identical to those observed in other populations of different ethnic backgrounds.
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PMID:Prevalence of autoantibodies in simplex and multiplex families of Brazilian insulin-dependent diabetic patients. 182 50

The relation between islet cell specific antibodies, other autoantibodies and antibodies to cow's milk proteins was studied in IDDM and pre-IDDM by analysing islet cell antibodies (ICA), insulin autoantibodies (IAA), anti-nuclear (ANA), anti-reticulin class IgA [ARA(IgA)], smooth muscle, anti-mitochondria, parietal cell (PCA), adrenal and thyroid antibodies and antibodies to cow's milk formula (CMF), beta-lactoglobulin (BLG) and bovine serum albumin (BSA) in a population based study with more than 650 children with newly diagnosed IDDM and more than 550 initially non-diabetic siblings. After adjustment for age a weak association was seen in the diabetic children between IAA and ANA but none between ICA and autoantibodies directed against the other organ-specific or non-organ-specific antigens. There was no significant difference in cow's milk antibodies between diabetic children with and without ICA or IAA. The siblings with ICA had higher CMF (IgA and IgM) antibody levels and BLG (IgA) antibody levels than the remaining siblings, but no such differences were found when comparing IAA-positive and negative siblings. Siblings positive for ICA had PCA more often than did the ICA-negative siblings, whereas siblings positive for both ICA and PCA had increased levels of antibodies against CMF, BLG and BSA. These findings indicate that the humoral islet cell-associated autoimmunity characteristic of recent-onset childhood IDDM is clearly restricted to the islet cells and not directly related to signs of other organ-specific or non-organ-specific autoimmunity. The observation of increased levels of antibodies to cow's milk proteins in siblings positive for ICA suggests that the immune response to cow's milk proteins may be related to the progressive autoimmune process resulting in beta-cell destruction and ultimately in the clinical manifestation of IDDM. Gastrointestinal autoimmune mechanisms may play a role in the pathogenesis of IDDM, and the association observed between combined ICA and PCA positivity and increased levels of antibodies to cow's milk proteins in the siblings implies that there may be an enhanced transfer of nutritional antigens across the gut barrier in these subjects.
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PMID:Relation between antibodies to islet cell antigens, other autoantigens and cow's milk proteins in diabetic children and unaffected siblings at the clinical manifestation of IDDM. The Childhood Diabetes in Finland Study Group. 887 52

A group of 230 type 1 (insulin-dependent) diabetic patients were screened for the presence of thyrogastric autoantibodies (aTPO and PCA) and magnesium depletion. Thirty-seven per cent presented with significant levels of 1 autoantibody and 7 per cent were positive for both. Exactly 25 per cent of the subjects had low levels of erythrocyte Mg (RBC-Mg < 5.5 mg/dl). Female patients were more prone to lower RBC-Mg and had a significant higher prevalence of aTPO and, although actually euthyroid, had a more pronounced history of thyroid disease. The presence of both antibodies was accompanied with the highest prevalence of low RBC-Mg. However, PCA positivity with hypergastrinaemia alone did not show a significant increase of the Mg depletion. The mechanisms involved in this phenomenon remain unclear but besides gender, duration of diabetes and the metabolic consequences of the disease, the presence of associated thyroid and gastric dysfunction can play a supplementary role in the maintenance of the chronic Mg problems in type 1 diabetes.
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PMID:Associated thyrogastric autoimmunity increases the prevalence of low erythrocyte magnesium in type 1 diabetes. 1061 85

The autoimmune attack in type 1 diabetes is not only targeted to beta cells. We assessed the prevalence of thyroid peroxidase (aTPO), parietal cell (PCA), antiadrenal (AAA) and endomysial antibodies (EmA-IgA), and of overt autoimmune disease in type 1 diabetes, in relation to gender, age, duration of disease, age at onset, beta-cell antibody status (ICA, GADA, IA2A) and HLA-DQ type. Sera from 399 type 1 diabetic patients (M/F: 188/211; mean age: 26 +/- 16 years; duration: 9 +/- 8 years) were tested for ICA, PCA, AAA and EmA-IgA by indirect immunofluorescence, and for IA2A (tyrosine phosphatase antibodies), GADA (glutamic acid decarboxylase-65 antibodies) and aTPO by radiobinding assays. The prevalence rates were: GADA 70%; IA2A, 44%; ICA, 39%; aTPO, 22%; PCA, 18%; EmA-IgA, 2%; and AAA, 1%. aTPO status was determined by female gender (beta = - 1.15, P = 0.002), age (beta = 0.02, P = 0.01) and GADA + (beta = 1.06, P = 0.02), but not by HLA-DQ type or IA2A status. Dysthyroidism (P < 0.0001) was more frequent in aTPO + subjects. PCA status was determined by age (beta = 0.03, P = 0.002). We also observed an association between PCA + and GADA + (OR = 1.9, P = 0.049), aTPO + (OR = 1.9, P = 0.04) and HLA DQA1*0501-DQB1*0301 status (OR = 2.4, P = 0.045). Iron deficiency anaemia (OR = 3.0, P = 0.003) and pernicious anaemia (OR = 40, P < 0.0001) were more frequent in PCA + subjects. EmA-IgA + was linked to HLA DQA1*0501-DQB1*0201 + (OR = 7.5, P = 0.039), and coeliac disease was found in three patients. No patient had Addison's disease. In conclusion, GADA but not IA2A indicate the presence of thyrogastric autoimmunity in type 1 diabetes. aTPO have a female preponderance, PCA are weakly associated with HLA DQA1*0501-DQB1*0301 and EmA-IgA + with HLA DQA1*0501-DQB1*0201.
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PMID:Beta-cell, thyroid, gastric, adrenal and coeliac autoimmunity and HLA-DQ types in type 1 diabetes. 1170 58

Type 1 diabetes mellitus (T1D) patients (G1; n=73) and first degree relatives with islet cell antibody (ICA) values of >or=10 JDF u twice or >or=20 JDF u one and loss of FPIR (G2; n=18) were screened for two other autoantibodies, anti-glutamic acid decarboxylase (GADA) and insulin autoantibodies (IAA), and for other organ-specific autoantibodies, anti-gastric parietal cell (anti-PCA) and anti-thyroid peroxidase (anti-TPO) as well. The two control groups consisted of healthy subjects (G3; n:55 and G4; n:13). In G1, positivity of ICA, GADA, IAA, anti-TPO and anti-PCA were 63%, 75.1%, 27.4%, 17.8% and 8.2%, respectively. In G2, positivity for GADA, IAA, anti-TPO and anti-PCA were 55.6%, 11.1%, 16.7% and 11.1%, respectively. None of the anti-TPO or anti-PCA positive cases had clinical or laboratory thyroid disease or pernicious anemia. Other organ specific antibodies, in case they accompany GADAand/or IAA in high risk individuals, result in higher risk for T1D. Moreover, this condition may indicate future potential for developing thyrogastric autoimmune diseases. In conclusion; autoantibodies are markers for autoimmune destruction in T1D, and for identification of subjects at risk for disease. Even at the time of diagnosis of T1D, screening for thyrogastric autoimmunity might be recommended for early detection of the relevant diseases.
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PMID:Organ specific autoantibodies in preclinical and early clinical type 1 diabetes in Turkey. 1757 23

The genetic basis of autoantibody production is largely unknown outside of associations located in the major histocompatibility complex (MHC) human leukocyte antigen (HLA) region. The aim of this study is the discovery of new genetic associations with autoantibody positivity using genome-wide association scan single nucleotide polymorphism (SNP) data in type 1 diabetes (T1D) patients with autoantibody measurements. We measured two anti-islet autoantibodies, glutamate decarboxylase (GADA, n = 2,506), insulinoma-associated antigen 2 (IA-2A, n = 2,498), antibodies to the autoimmune thyroid (Graves') disease (AITD) autoantigen thyroid peroxidase (TPOA, n = 8,300), and antibodies against gastric parietal cells (PCA, n = 4,328) that are associated with autoimmune gastritis. Two loci passed a stringent genome-wide significance level (p<10(-10)): 1q23/FCRL3 with IA-2A and 9q34/ABO with PCA. Eleven of 52 non-MHC T1D loci showed evidence of association with at least one autoantibody at a false discovery rate of 16%: 16p11/IL27-IA-2A, 2q24/IFIH1-IA-2A and PCA, 2q32/STAT4-TPOA, 10p15/IL2RA-GADA, 6q15/BACH2-TPOA, 21q22/UBASH3A-TPOA, 1p13/PTPN22-TPOA, 2q33/CTLA4-TPOA, 4q27/IL2/TPOA, 15q14/RASGRP1/TPOA, and 12q24/SH2B3-GADA and TPOA. Analysis of the TPOA-associated loci in 2,477 cases with Graves' disease identified two new AITD loci (BACH2 and UBASH3A).
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PMID:Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. 2182 93

Autoantibodies targeting the H+/K+-ATPase proton pump of the gastric parietal cell (parietal cell antibodies [PCA]) are diagnostic of atrophic body gastritis (ABG) leading to pernicious anemia (PA). PCA, ABG, and PA occur in increased frequency in patients with type 1 diabetes and their relatives and are considered "minor" components of forms of autoimmune polyglandular syndrome (APS). A customized radioimmunoprecipitation assay was applied to 6,749 samples from the Type 1 Diabetes Genetics Consortium to measure ATP4A autoreactivity. Autoantibody prevalence was correlated with variants in HLA class II, PTPN22, and CTLA4 genes. With an ATP4A radioimmunoprecipitation assay, PCA were detected in sera from 20.9% of affected individuals. PCA prevalence increased with age and was greater in females (25.3%) than males (16.5%) and among Hispanics (36.3%) and blacks (26.2%) compared with non-Hispanic whites (20.8%) and Asians (16.7%). PCA and other organ-specific autoantibodies GAD65, IA-2, thyroid peroxidase (TPO), 21-hydroxylase (21-OH), and transglutaminase (TG) clustered within families with heritability estimates from 71 to 95%. PCA clustered with TPO, 21-OH, and persistent GAD65 autoantibodies but not with celiac (TG) or IA-2 autoantibodies. PCA-positive subjects showed an increased frequency of DRB1*0404, DPB1*0201, and PTPN22 R620W (rs2476601-T) and a decreased frequency of DRB1*0101, DPB1*0301, and CTLA4 CT60 (rs3087243-T). Genetic variants accounted for 4-5% of the heritable risk for PCA. The same alleles were associated with other autoantibody phenotypes in a consistent pattern. Whereas most of the heritable risk for PCA and other antibodies reflects genetic effects that are tissue specific, parietal cell autoimmunity is a major pathogenetic contributor in APS2.
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PMID:ATPase4A Autoreactivity and Its Association With Autoimmune Phenotypes in the Type 1 Diabetes Genetics Consortium Study. 2640 69