Abstract:
:To study the immune response to glutamic acid decarboxylase (GAD) in insulin-dependent diabetes mellitus, monoclonal GAD antibodies after fusion of splenocytes from a nondiabetes-susceptible BALB/c mouse immunized with human recombinant GAD65 were generated. Of the 44 monoclonals, 35 are specific for the GAD65 isoform, whereas 9 also react with GAD67. Some 37 monoclonals, including all GAD65/67 reactive antibodies, react with GAD by Western blot analysis. The remaining 7 GAD65 monoclonals bind GAD only in an immunoprecipitation assay, which implies that they target epitopes dependent on the conformation of the GAD molecule. The 125I-GAD binding of the GAD65 monoclonals reactive on Western blotting was significantly diminished by all 3 sera from Stiff-man syndrome patients but only by 3/30 (10%) sera from type 1 diabetic patients. In contrast, the 7 monoclonal antibodies reactive with a conformation-dependent GAD epitope were competitive with 83% of GAD-autoantibody-positive sera from these diabetic patients. Using chimeric GAD65/67 proteins, the epitope region targeted by these monoclonals was mapped to the middle of GAD65 (amino acids 221-442). This central conformation-dependent GAD region was also targeted by sera from patients with type 1 diabetes. In conclusion, our data show that even after common immunization of a nondiabetes-susceptible mouse strain, monoclonal were obtained which preferentially react with the GAD65 linear amino-terminus (amino acids 4-17) and a conformation-dependent region located in the middle of GAD targeted by autoantibodies, indicating that this GAD region is not restricted to the autoimmune response associated with the Stiff-man syndrome and the beta-cell destruction in type 1 diabetes mellitus.
journal_name
Acta Diabetoljournal_title
Acta diabetologicaauthors
Ziegler B,Schlosser M,Lühder F,Strebelow M,Augstein P,Northemann W,Powers AC,Ziegler Mdoi
10.1007/BF02048548subject
Has Abstractpub_date
1996-09-01 00:00:00pages
225-31issue
3eissn
0940-5429issn
1432-5233journal_volume
33pub_type
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,meta分析,评审
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pub_type: 杂志文章
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abstract::Selective loss of capillary pericytes occurs early and specifically in diabetic retinopathy. We have investigated whether blood derivatives from patients with long-term type 1 (insulin-dependent) diabetes and no retinopathy differ from those with retinopathy and/or non-diabetic controls in their ability to stimulate D...
journal_title:Acta diabetologica
pub_type: 杂志文章
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journal_title:Acta diabetologica
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doi:10.1007/s00592-007-0235-9
更新日期:2007-03-01 00:00:00
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journal_title:Acta diabetologica
pub_type: 临床试验,杂志文章
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journal_title:Acta diabetologica
pub_type: 杂志文章
doi:10.1007/s005920050073
更新日期:1997-10-01 00:00:00
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pub_type: 杂志文章
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doi:10.1007/s00592-008-0044-9
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pub_type: 杂志文章,多中心研究
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pub_type: 杂志文章
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更新日期:2016-06-01 00:00:00
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journal_title:Acta diabetologica
pub_type: 杂志文章,评审
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journal_title:Acta diabetologica
pub_type: 杂志文章
doi:10.1007/BF00569418
更新日期:1996-07-01 00:00:00
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journal_title:Acta diabetologica
pub_type: 杂志文章
doi:10.1007/s00592-017-1066-y
更新日期:2018-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s005920200020
更新日期:2002-06-01 00:00:00
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更新日期:2000-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s00592-013-0515-5
更新日期:2014-01-01 00:00:00
abstract::The aim was to investigate the long-term incidence of proliferative diabetic retinopathy (PDR), and progression and regression of diabetic retinopathy (DR) and associated risk factors in young Danish patients with Type 1 diabetes mellitus. In 1987-89, a pediatric cohort involving approximately 75 % of all children wit...
journal_title:Acta diabetologica
pub_type: 杂志文章
doi:10.1007/s00592-013-0527-1
更新日期:2014-01-01 00:00:00
abstract::Autonomic nervous dysfunction is considered to be one of the mechanisms of metabolic syndrome (MetS). The aim of this study is to investigate whether resting heart rate, a marker of autonomic nervous dysfunction, is a predictor of MetS in apparently healthy non-obese [body mass index (BMI) <25 kg/m(2)] Japanese men. T...
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pub_type: 杂志文章
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更新日期:2014-02-01 00:00:00