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Epitope Analysis of GAD65 Binding in both Cord Blood and at the Time of Clinical Diagnosis of Childhood Type 1 Diabetes.

Elfving, Maria LU ; Lindberg, Bengt LU ; Lynch, Kristian LU ; Ivarsson, Sten LU ; Lernmark, Åke LU and Hampe, C. S. (2007) In Hormone and Metabolic Research 39(11). p.790-796
Abstract
The GAD65 epitope immunoglobulin binding pattern in cord blood of children (n=37), who later developed type 1 diabetes at 3.2-14.9 years of age, was analyzed. First, the binding at diagnosis was compared with that in the cord blood serum. The next comparison was between the cord blood serum and the mothers' serum taken at delivery. Basal GAD65 binding levels were determined in Protein A Sepharose-based radio-binding assays with S-35-labeled human and rat GAD65, rat GAD67 and GAD65/67 fusion proteins representing N-terminal (N), middle (M) and C-terminal (C) epitopes. In the first comparison, 28/37 children had GAD65 binding above 2.44 relative units (RU) (upper three quartiles), representing a marked increase from birth in the binding to... (More)
The GAD65 epitope immunoglobulin binding pattern in cord blood of children (n=37), who later developed type 1 diabetes at 3.2-14.9 years of age, was analyzed. First, the binding at diagnosis was compared with that in the cord blood serum. The next comparison was between the cord blood serum and the mothers' serum taken at delivery. Basal GAD65 binding levels were determined in Protein A Sepharose-based radio-binding assays with S-35-labeled human and rat GAD65, rat GAD67 and GAD65/67 fusion proteins representing N-terminal (N), middle (M) and C-terminal (C) epitopes. In the first comparison, 28/37 children had GAD65 binding above 2.44 relative units (RU) (upper three quartiles), representing a marked increase from birth in the binding to human GAD65 (p < 0.0001), rat GAD65 (p < 0.0001), N- (p = 0.04), M- (p < 0.0001), C- (p=0.001), and M + C-epitopes (p < 0.0001), but not to rat GAD67. At birth, 9/37 had GAD65 binding above 1.56 RU (upper quartile) demonstrating that their binding of human S-35-GAD65 was higher in cord blood than in the mother (p=0.008). Higher cord blood binding was also observed for the N- (p=0.02) terminal epitope but not for rat GAD65, rat GAD67, and the remaining epitopes. These data suggest that differences in the epitope GAD65 binding between mother and child at birth are limited. In contrast, the epitope pattern at diagnosis differed from that at birth, supporting the view that disease-associated epitopes develop between birth and diagnosis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cord blood islet autoantibodies, epitope analysis, diabetes, mellitus, glutamic acid decarboxylase, type 1 (insulin-dependent)
in
Hormone and Metabolic Research
volume
39
issue
11
pages
790 - 796
publisher
Georg Thieme Verlag
external identifiers
  • scopus:36749078111
  • wos:000251545700004
ISSN
1439-4286
DOI
10.1055/s-2007-992128
language
English
LU publication?
yes
id
199a5506-7104-48ba-8044-4ec1be4abc21 (old id 1140883)
date added to LUP
2008-08-01 13:30:55
date last changed
2017-01-01 06:43:21
@article{199a5506-7104-48ba-8044-4ec1be4abc21,
  abstract     = {The GAD65 epitope immunoglobulin binding pattern in cord blood of children (n=37), who later developed type 1 diabetes at 3.2-14.9 years of age, was analyzed. First, the binding at diagnosis was compared with that in the cord blood serum. The next comparison was between the cord blood serum and the mothers' serum taken at delivery. Basal GAD65 binding levels were determined in Protein A Sepharose-based radio-binding assays with S-35-labeled human and rat GAD65, rat GAD67 and GAD65/67 fusion proteins representing N-terminal (N), middle (M) and C-terminal (C) epitopes. In the first comparison, 28/37 children had GAD65 binding above 2.44 relative units (RU) (upper three quartiles), representing a marked increase from birth in the binding to human GAD65 (p &lt; 0.0001), rat GAD65 (p &lt; 0.0001), N- (p = 0.04), M- (p &lt; 0.0001), C- (p=0.001), and M + C-epitopes (p &lt; 0.0001), but not to rat GAD67. At birth, 9/37 had GAD65 binding above 1.56 RU (upper quartile) demonstrating that their binding of human S-35-GAD65 was higher in cord blood than in the mother (p=0.008). Higher cord blood binding was also observed for the N- (p=0.02) terminal epitope but not for rat GAD65, rat GAD67, and the remaining epitopes. These data suggest that differences in the epitope GAD65 binding between mother and child at birth are limited. In contrast, the epitope pattern at diagnosis differed from that at birth, supporting the view that disease-associated epitopes develop between birth and diagnosis.},
  author       = {Elfving, Maria and Lindberg, Bengt and Lynch, Kristian and Ivarsson, Sten and Lernmark, Åke and Hampe, C. S.},
  issn         = {1439-4286},
  keyword      = {cord blood islet autoantibodies,epitope analysis,diabetes,mellitus,glutamic acid decarboxylase,type 1 (insulin-dependent)},
  language     = {eng},
  number       = {11},
  pages        = {790--796},
  publisher    = {Georg Thieme Verlag},
  series       = {Hormone and Metabolic Research},
  title        = {Epitope Analysis of GAD65 Binding in both Cord Blood and at the Time of Clinical Diagnosis of Childhood Type 1 Diabetes.},
  url          = {http://dx.doi.org/10.1055/s-2007-992128},
  volume       = {39},
  year         = {2007},
}