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:
https://lup.lub.lu.se/record/1140900
- author
- Jonson, CO
; Lernmark, Åke
LU
; Ludvigsson, J
; Rutledge, EA
; Hinkkanen, A
and Faresjö, M
- organization
- publishing date
- 2007
- 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
- pmid:17659059
- 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
- 2016-04-04 13:04:27
- date last changed
- 2022-01-29 23:46:35
@article{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}},
keywords = {{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}},
doi = {{10.1111/j.1399-5448.2007.00245.x}},
volume = {{8}},
year = {{2007}},
}