The importance of CTLA-4 polymorphism and Human leukocyte antigen genotype for the induction of diabetes-associated cytokine response in healthy school children
2007 (English)In: Pediatric Diabetes, ISSN 1399-543X (print) 1399-5448 (online), Vol. 8, no 4, 185-192 p.Article in journal (Refereed) Published
Background: 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.
Place, publisher, year, edition, pages
2007. Vol. 8, no 4, 185-192 p.
CTLA-4, cytokines, HLA, SNP, type 1 diabetes mellitus
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-12876DOI: 10.1111/j.1399-5448.2007.00245.xOAI: oai:DiVA.org:liu-12876DiVA: diva2:17266