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The importance of CTLA-4 polymorphism and human leukocyte antigen genotype for the induction of diabetes-associated cytokine response in healthy school children.

Jonson, CO; Lernmark, Åke LU ; Ludvigsson, J; Rutledge, EA; Hinkkanen, A and Faresjö, M (2007) In Pediatr Diabetes 8(4). p.185-192
Abstract
Type 1 diabetes (T1D) is an autoimmune disease associated with the destruction of pancreatic β cells and genetically linked to human leukocyte antigen (HLA) class II DR3-DQ2 and DR4-DQ8 haplotypes. The +49A/G polymorphism of the immunoregulatory cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene is also associated with T1D. Genetic and environmental risk factors precede the onset of T1D, which is characterized by a T helper 1 cell-dominating cytokine response to diabetes-related autoantigens. Aim: 



To investigate immunological differences between healthy children with and without CTLA-4 +49A/G and HLA genetic susceptibility for T1D. Study design: 



Young, 7-15 years of age, healthy subjects (n = 58) were... (More)
Type 1 diabetes (T1D) is an autoimmune disease associated with the destruction of pancreatic β cells and genetically linked to human leukocyte antigen (HLA) class II DR3-DQ2 and DR4-DQ8 haplotypes. The +49A/G polymorphism of the immunoregulatory cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene is also associated with T1D. Genetic and environmental risk factors precede the onset of T1D, which is characterized by a T helper 1 cell-dominating cytokine response to diabetes-related autoantigens. Aim: 



To investigate immunological differences between healthy children with and without CTLA-4 +49A/G and HLA genetic susceptibility for T1D. Study design: 



Young, 7-15 years of age, healthy subjects (n = 58) were investigated to test whether CTLA-4 +49A/G genotype was associated with enzyme-linked immunospot assay T-cell responses to T1D-related autoantigens. Because T1D is primarily HLA-DQ associated, we stratified the healthy subjects by HLA genotypes associated with the disease. Results: 



Peptide of heat shock protein 60 induced a higher interferon-γ (IFN-γ) response in subjects with risk-associated CTLA-4 polymorphism (GG genotype) (p = 0.02) while glutamic acid decarboxylase 65-induced interleukin-4 (IL-4) secretion was lower in GG genotype subjects (p = 0.02). Conclusion: 



The increased IFN-γ response and lower IL-4 response toward diabetes-related autoantigens shown in CTLA-4 +49 GG risk subjects show a possible mechanism for the association between CTLA-4 and T1D. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CTLA-4, cytokines, HLA, SNP, type 1 diabetes mellitus
in
Pediatr Diabetes
volume
8
issue
4
pages
185 - 192
external identifiers
  • Scopus:34547128874
DOI
10.1111/j.1399-5448.2007.00245.x
language
English
LU publication?
yes
id
a6d22590-ac11-45c8-940e-503efb66f5e9 (old id 1140900)
date added to LUP
2008-08-14 12:07:21
date last changed
2016-10-13 04:52:53
@misc{a6d22590-ac11-45c8-940e-503efb66f5e9,
  abstract     = {Type 1 diabetes (T1D) is an autoimmune disease associated with the destruction of pancreatic β cells and genetically linked to human leukocyte antigen (HLA) class II DR3-DQ2 and DR4-DQ8 haplotypes. The +49A/G polymorphism of the immunoregulatory cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene is also associated with T1D. Genetic and environmental risk factors precede the onset of T1D, which is characterized by a T helper 1 cell-dominating cytokine response to diabetes-related autoantigens. Aim: <br/><br>
<br/><br>
To investigate immunological differences between healthy children with and without CTLA-4 +49A/G and HLA genetic susceptibility for T1D. Study design: <br/><br>
<br/><br>
Young, 7-15 years of age, healthy subjects (n = 58) were investigated to test whether CTLA-4 +49A/G genotype was associated with enzyme-linked immunospot assay T-cell responses to T1D-related autoantigens. Because T1D is primarily HLA-DQ associated, we stratified the healthy subjects by HLA genotypes associated with the disease. Results: <br/><br>
<br/><br>
Peptide of heat shock protein 60 induced a higher interferon-γ (IFN-γ) response in subjects with risk-associated CTLA-4 polymorphism (GG genotype) (p = 0.02) while glutamic acid decarboxylase 65-induced interleukin-4 (IL-4) secretion was lower in GG genotype subjects (p = 0.02). Conclusion: <br/><br>
<br/><br>
The increased IFN-γ response and lower IL-4 response toward diabetes-related autoantigens shown in CTLA-4 +49 GG risk subjects show a possible mechanism for the association between CTLA-4 and T1D.},
  author       = {Jonson, CO and Lernmark, Åke and Ludvigsson, J and Rutledge, EA and Hinkkanen, A and Faresjö, M},
  keyword      = {CTLA-4,cytokines,HLA,SNP,type 1 diabetes mellitus},
  language     = {eng},
  number       = {4},
  pages        = {185--192},
  series       = {Pediatr Diabetes},
  title        = {The importance of CTLA-4 polymorphism and human leukocyte antigen genotype for the induction of diabetes-associated cytokine response in healthy school children.},
  url          = {http://dx.doi.org/10.1111/j.1399-5448.2007.00245.x},
  volume       = {8},
  year         = {2007},
}