The natural history and predictive value of Mr 64,000 autoantibodies for insulin-dependent diabetes mellitus

Atkinson, Mark A.; Maclaren, Noel K.; Holmes, Lynn; Scharp, David W.; Lacy, Paul E.; Riley, William J.

doi:10.1016/s0896-8411(09)90008-7

Cited by 19 publications

(19 citation statements)

References 9 publications

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“…GAD 65 antibodies were detected in a total of 33 (75%) of the prediabetic patients in the first sample available 3-85 mo before clinical onset of disease, a result consistent with earlier studies (39,40). IA2 antibodies were detected in 20/44 (45%) of the prediabetic individuals.…”

Section: Autoantibodies To the 38-kd Antigen Are Present In A Subgrousupporting

confidence: 89%

“…Both GAD 65 and IA2 antibodies were detected at clinical onset in a child, who developed type 1 diabetes as early as 0.8 yr of age, and 38-kD antibodies were detected in a child who developed diabetes at 1.3 yr of age. Since the duration of ␤ cell autoimmunity in those very young children must have been significantly shorter than is often the case in older individuals (39,40), this result suggest that all three proteins may be targets of primary rather than secondary autoimmune processes directed to the ␤ cell in the human disease. This notion is supported by the appearance of antibodies to all three antigens several years before the clinical onset of type 1 diabetes.…”

Section: Discussionmentioning

confidence: 93%

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Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes.

Aanstoot

Kang²,

Kim³

et al. 1996

J. Clin. Invest.

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Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD 65 , and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic ␤ cell destruction and development of type 1 diabetes. Here we identify a third islet cell autoantigen, a novel 38-kD protein, which is specifically immunoprecipitated with sera from a subset of prediabetic individuals and newly diagnosed type 1 diabetic patients. The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD 65 and IA2. Removal of N-linked carbohydrates results in a protein of 22,000 M r . Glima 38 autoantibodies were detected in 16/86 (19%) of newly diagnosed patients, including three very young children, who had a rapid onset of disease, and in 6/44 (14%) of prediabetic individuals up to several years before clinical onset. The cumulative incidence of GAD 65 and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD 65

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Section: Autoantibodies To the 38-kd Antigen Are Present In A Subgrousupporting

confidence: 89%

Section: Discussionmentioning

confidence: 93%

Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes.

Aanstoot

Kang²,

Kim³

et al. 1996

J. Clin. Invest.

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“…T he 64,000-/W r protein (1), recently identified as GAD (2), is the major antigen for autoantibodies in sera from IDDM patients (3)(4)(5)(6)(7). GAD catalyzes the formation of GABA, a major neuroinhibitor in the CNS.…”

mentioning

confidence: 99%

“…GAD also is expressed in the islets of Langerhans, although the significance of islet GAD and GABA is unclear (8). Antibodies against the 64,000-M r autoantigen or GAD are found in sera in 75-96% of patients at the time of clinical onset (3)(4)(5)(6)(7)9), and have been demonstrated up to 8 yr before onset (3,6,9). In contrast, GAD antibodies are found in <2% of sera from healthy individuals (3)(4)(5)(6)(7)9).…”

mentioning

confidence: 99%

Recombinant Glutamic Acid Decarboxylase (Representing the Single Isoform Expressed in Human Islets) Detects IDDM-Associated 64,000-Mr Autoantibodies

et al. 1992

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GAD is an autoantigen in IDDM. Molecular cloning and specific antibodies allowed us to demonstrate that only the lower M r GAD64 isoform is expressed in human islets, in contrast to human brain, rat islets, and rat brain, all of which express both GAD64 and GAD67. Expression of the human islet GAD64 isoform in COS-7 and BHK cells resulted in an enzymatically active rGAD64, which is immunoreactive with diabetic sera comparable with that of the islet 64,000-Af r autoantigen. Immunoprecipitation analyses showed that 21/28 (75%) IDDM sera had rGAD64 antibodies compared with only 1/59 (1.7%) of the healthy control sera. In immunoblot analyses, an SMS serum-but only 1/10 randomly selected IDDM sera-recognized the blotted rGAD64 without relation to immunoprecipitation titers. In conclusion, only the GAD64 isoform is expressed in human islets, in contrast to rat islets, which also express the GAD67 isoform. The immunological properties of human rGAD64 are comparable with the native 64,000-M r islet autoantigen, allowing further studies of the immunopathogenesis of IDDM. Diabetes 41:1355-59, 1992

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“…It is one of the major autoantigens in type 1 (insulin-dependent) diabetes, an autoimmune disease resulting from the destruction of insulin-producing β cells in the pancreas [28,29]. It has been demonstrated that many new-onset type 1 diabetic patients have autoantibodies against GAD65, with the presence of anti-GAD65 antibodies now serving as an important marker for the prediction and diagnosis of type 1 diabetes [30][31][32]. The identification of GAD as a major autoantigen in type 1 diabetes may also present unique opportunities for the development of novel preventative therapies against the disease.…”

Section: Introductionmentioning

confidence: 99%

A novel expression platform for the production of diabetes-associated autoantigen human glutamic acid decarboxylase (HGAD65)

Brandsma

Tremblay

2008

Journal of Biotechnology

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Background: Human glutamic acid decarboxylase 65 (hGAD65) is a key autoantigen in type 1 diabetes, having much potential as an important marker for the prediction and diagnosis of type 1 diabetes, and for the development of novel antigen-specific therapies for the treatment of type 1 diabetes. However, recombinant production of hGAD65 using conventional bacterial or mammalian cell culture-based expression systems or nuclear transformed plants is limited by low yield and low efficiency. Chloroplast transformation of the unicellular eukaryotic alga Chlamydomonas reinhardtii may offer a potential solution.

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The natural history and predictive value of Mr 64,000 autoantibodies for insulin-dependent diabetes mellitus

Cited by 19 publications

References 9 publications

Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes.

Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes.

Recombinant Glutamic Acid Decarboxylase (Representing the Single Isoform Expressed in Human Islets) Detects IDDM-Associated 64,000-Mr Autoantibodies

A novel expression platform for the production of diabetes-associated autoantigen human glutamic acid decarboxylase (HGAD65)

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