Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10.

Karlsen, Allan E.; Hagopian, William; Grubin, Catherine E.; Dube, Syamalima; Distèche, Christine M.; Adler, David A.; Bärmeier, Heike; Mathewes, Shannon; Grant, Francis James; Foster, Don; Lernmark, Åke

doi:10.1073/pnas.88.19.8337

Cited by 250 publications

(164 citation statements)

References 41 publications

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“…In type 1 diabetes, autoantibodies against pancreatic antigens such as the 65 kD isoform of glutamic acid decarboxylase (GAD 65 ) [1], insulin and the tyrosine phosphatase-like protein IA-2 (IA-2) [2] may be detected long before clinical onset of the disease, and they are often present at diagnosis [3; 4; 5; 6; 7]. Even though autoantibodies are indicators of an ongoing immune process, it has not been established whether they contribute to the pathogenesis of the disease or if they are markers of an ongoing destructive process.…”

Section: Introductionmentioning

confidence: 99%

GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response

Chéramy

Skoglund

Johansson

et al. 2010

Clinical Immunology

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, GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD (65) AbstractWe have previously shown that two injections of 20 μg GAD-alum to recent onset type 1 diabetic children induced GADA levels in parallel to preservation of insulin secretion. Here we investigated if boosted GADA induced changes in IgG1, 2, 3 and 4 subclass distributions or affected GAD 65 enzyme activity. We further studied the specific effect of GAD-alum through analyses of IA-2A, tetanus toxoid and total IgE antibodies. Serum from children receiving GAD-alum or placebo was collected pre-treatment and after 3, 9, 15 and 21 months.At 3 month a reduced percentage of IgG1 and increased IgG3/IgG4 were detected in GADalum treated. Further, IA-2A, IgE and tetanus toxoid antibodies, as well as GAD 65 enzyme activity, were unaffected confirming the specific effect of treatment. In the GAD-alum group, higher pre-treatment GADA were associated to more pronounced C-peptide preservation. The induced IgG3/IgG4 and reduced IgG1 suggest a Th2 deviation of the immune response.

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Section: Introductionmentioning

confidence: 99%

GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response

Chéramy

Skoglund

Johansson

et al. 2010

Clinical Immunology

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“…GABA is synthesized by glutamic acid decarboxylase (GAD) and could be involved in islet-cell development. GAD has been associated with Type I diabetes in humans [90,91] and in non-obese diabetic (NOD) mice [92,93,94]. GAD expression in islets is inhibited by IL-1β exposure [95].…”

Section: Cellular Defence (Two Proteins)mentioning

confidence: 99%

IL-1β induced protein changes in diabetes prone BB rat islets of Langerhans identified by proteome analysis

Sparre

Bjerre-Christensen

Larsen³

et al. 2002

Diabetologia

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Aims/hypothesis. Type I (insulin-dependent) diabetes mellitus is characterized by selective destruction of the insulin producing beta cells. Interleukin-1β (IL-1β) modulates the beta-cell function, protein synthesis, energy production and causes apoptosis. We have previously shown changes in the expression of 82 out of 1 815 protein spots detected by two dimensional gel electrophoresis in IL-1β exposed diabetes prone Bio Breeding (BB-DP) rat islets of Langerhans in vitro. The aim of this study was to identify the proteins in these 82 spots by mass spectrometry and compare these changes with those seen in IL-1β exposed Wistar Furth (WF) rat islets. Methods. The 82 protein spots, that changed expression after IL-1β exposure, were all re-identified on preparative gels of 200 000 neonatal WF rat islets, cut out and subjected to mass spectrometry for identification.Results. Forty-five different proteins were identified from 51 spots and grouped according to function: (i) energy transduction and redox potentials; (ii) glycolytic and Krebs cycle enzymes; (iii) protein, DNA and RNA synthesis, chaperoning and protein folding; (iv) signal transduction, regulation, differentiation and apoptosis; (v) cellular defence; and (vi) other functions. Comparison of IL-1β exposed BB-DP and WF islets showed common changes in 14 proteins and several proteins influencing similar pathways, suggesting that similar routes in the two strains lead to beta-cell destruction. Conclusion/interpretation. We demonstrate that proteome analysis is a powerful tool to identify proteins and pathways in BB-DP rat islets exposed to IL-1β. [Diabetologia (2002) 45:1550-1561

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“…respectively (Brilliant 1990;Karlsen 1991;Bu & Tobin 1994;Erlander 1991). Although the two isoforms display a high similarity in their amino acid sequences, differences are found in their interaction with the co-factor pyridoxal-5ƍ-phosphate and in enzyme kinetics for GABA production (Battaglioli 2003).…”

Section: Glutamic Acid Decarboxylasementioning

confidence: 99%

MS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus‐specific IgG antibodies produced in vivo and by CSF B cells in vitro

Skorstad

Vandvik

Vartdal

et al. 2009

Euro J of Neurology

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Background: Intrathecal synthesis of oligoclonal IgG antibodies against measles virus (MeV), varicella zoster virus (VZV) and herpes simplex virus type‐1 (HSV‐1) is a characteristic feature multiple sclerosis (MS). Methods: We have used isoelectric focusing‐immunoblot to define the clonal patterns of IgG and of IgG antibodies to MeV, VZV and HSV‐1 in supernatants of in vitro cultures of peripheral blood lymphocytes (PBL) and cerebrospinal fluid (CSF) cells and in sera and CSF from three patients with MS and three patients with clinically isolated syndromes (CIS) suspective of demyelinating disease. Results: In vitro synthesis of IgG by PBL was not detected in any patient. In contrast, in vitro synthesis by CSF cells of oligoclonal IgG and oligoclonal IgG antibodies to one or two of the three viruses tested was observed in all six patients. The clonal patterns of the in vitro synthesized IgG and virus specific IgG differed to varying extent from those synthesized intrathecally in vivo. However, in each patient, the in vitro and in vivo intrathecally produced antibodies displayed specificity for the same viruses. The addition of B cell activating factor (BAFF) had no effect on the amounts or clonal patterns of either total IgG or virus‐specific IgG produced by CSF cells in vitro. Conclusion: Virus specific B cells capable of spontaneous IgG synthesis are clonally expanded in the CSF of patients with MS. The B‐cell repertoire in CSF samples is only partially representative of the intrathecal B‐cell repertoire.

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Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10.

Cited by 250 publications

References 41 publications

GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response

GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response

IL-1β induced protein changes in diabetes prone BB rat islets of Langerhans identified by proteome analysis

MS and clinically isolated syndromes: Shared specificity but diverging clonal patterns of virus‐specific IgG antibodies produced in vivo and by CSF B cells in vitro

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