Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type.

Hagopian, William; Karlsen, Allan E.; Gottsäter, Anders; Landin‐Olsson, Mona; Grubin, Catherine E.; Sundkvist, Göran; Petersen, Jacob Sten; Boel, Esper; Dyrberg, Thomas; Lernmark, Åke

doi:10.1172/jci116195

Cited by 206 publications

(116 citation statements)

References 36 publications

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“…It has been known since the early days of ICA measurements that diabetic patients who failed oral hypoglycemic agents often had ICAs (13). These early observations were confirmed and extended when standardized methods to measure GAD65Abs became available (58). The most common DAA found in this group is GAD65Ab, which is found in ϳ5-10% of subjects; ϳ2-4% of adults have IA-2Ab and Ͻ1% have IAA.…”

Section: Diabetes Classification and Daasmentioning

confidence: 79%

Autoantibodies in Diabetes

et al. 2005

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Islet cell autoantibodies are strongly associated with the development of type 1 diabetes. The appearance of autoantibodies to one or several of the autoantigens-GAD65, IA-2, or insulin-signals an autoimmune pathogenesis of ␤-cell killing. A ␤-cell attack may be best reflected by the emergence of autoantibodies dependent on the genotype risk factors, isotype, and subtype of the autoantibodies as well as their epitope specificity. It is speculated that progression to ␤-cell loss and clinical onset of type 1 diabetes is reflected in a developing pattern of epitopespecific autoantibodies. Although the appearance of autoantibodies does not follow a distinct pattern, the presence of multiple autoantibodies has the highest positive predictive value for type 1 diabetes. In the absence of reliable T-cell tests, dissection of autoantibody responses in subjects of genetic risk should prove useful in identifying triggers of islet autoimmunity by examining seroconversion and maturation of the autoantibody response that may mark time to onset of type 1 diabetes. The complexity of the disease process is exemplified by multiple clinical phenotypes, including autoimmune diabetes masquerading as type 2 diabetes in youth and adults. Autoantibodies may also provide prognostic information in clinically heterogeneous patient populations when examined longitudinally. Diabetes 54 (Suppl. 2):S52-S61, 2005

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Section: Diabetes Classification and Daasmentioning

confidence: 79%

Autoantibodies in Diabetes

et al. 2005

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“…IAA. In the exploratory analysis, the unadjusted frequency of IAA increased with the number of class I alleles of INS VNTR: 15% of III/III patients (95% CI 0 -30), 30% of I/III patients (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), and 40% of I/I patients (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) were positive for IAA. Unadjusted frequencies of IAA were higher in DQ8-positive than in DQ8-negative patients: 27% of patients with no DQ8 haplotypes (95% CI 20 -34), 41% of patients with one DQ8 haplotype (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46), and 42% of patients with two DQ8 haplotypes (26 -57) were positive for IAA.…”

Section: Resultsmentioning

confidence: 99%

“…Glutamate decarboxylase autoantibodies. Antibodies to radiolabeled human Mr 65,000 glutamate decarboxylase (GADA) were quantified by fluid-phase immunoprecipitation assay using fluorographic densitometry as described (13,28) except that for 15-to 35-year-olds, GAD65 were radiolabeled by coupled in vitro transcription and translation, as described (29,30). The two assay formats correlate well, and autoantibody levels are expressed as GADA index as described elsewhere (29), using the WHO-Juvenile Diabetes Foundation (JDF) standard (31) as the positive control.…”

Section: Insulin Gene Vntr (Iddm2)mentioning

confidence: 99%

Genetic Effects on Age-Dependent Onset and Islet Cell Autoantibody Markers in Type 1 Diabetes

et al. 2002

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Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0 -34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P ‫؍‬ 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P ‫؍‬ 0.03) and with INS VNTR (P ‫؍‬ 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P ‫؍‬ 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P ‫؍‬ 0.04), and all four autoantibody markers (P ‫؍‬ 0.004). The CTLA-4 3 end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development. Diabetes 51: 1346 -1355, 2002

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“…Such a mechanism would explain the lack of GAD-ab in longterm NIDDM patients. The commencement of NIDDM is not associated with GAD-ab; GAD-ab in "NIDDM patients" indicate the diagnosis of IDDM [41,42].…”

Section: Discussionmentioning

confidence: 94%

Glutamic acid decarboxylase antibodies, autonomic nerve antibodies and autonomic neuropathy in diabetic patients

Sundkvist¹,

Velloso²,

K�mpe³

et al. 1994

Diabetologia

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SummaryTo clarify whether GAD-ab are associated with diabetic autonomic neuropathy and/or complement fixing antibodies against sympathetic ganglia, adrenal medulla, and vagus nerve, we examined 133 diabetic patients (95 with IDDM). GAD-ab were determined by a radioligand binding assay using in vitro expression of recombinant GAD-65 whereas sympathetic ganglia antibodies, adrenal medulla antibodies, vagus nerve, and ICA were evaluated by indirect immunofluorescence assays. Autonomic nerve function was evaluated by objective tests (heart rate reactions to deep breathing and to tilt). In the total material of 133 patients, GAD-ab were detected in 36 patients, all of whom had IDDM. The frequency of GADab was similar (38 %) in IDDM patients with and without signs of autonomic neuropathy (21 of 55 vs 15 of 40). In addition, there were no significant associations between GAD-ab and autonomic nerve antibodies; GAD-ab were detected in 9 of 21 (43 %) of patients with and in 27 of 112 (24 %) of patients without sympathetic ganglia antibodies, in 5 of 15 (33 %) of patients with and 31 of 118 (26 %) without adrenal medulla antibodies, and in 5 of 15 (33 % ) with and 31 of 118 (26 %) of patients without vagus nerve antibodies. The frequency of ICA, however, was significantly increased in patients with sympathetic ganglia antibodies compared with those without sympathetic ganglia antibodies (10 of 21 [48 %] vs 21 of 112 [19 %];p < 0.01). In conclusion, GAD-ab were neither associated with disturbed autonomic nerve function nor with antibodies against autonomic nerve structures. [Diabetologia (1994) 37: 293-299]

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Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type.

Cited by 206 publications

References 36 publications

Autoantibodies in Diabetes

Autoantibodies in Diabetes

Genetic Effects on Age-Dependent Onset and Islet Cell Autoantibody Markers in Type 1 Diabetes

Glutamic acid decarboxylase antibodies, autonomic nerve antibodies and autonomic neuropathy in diabetic patients

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