Effect of HLA genotype or CTLA-4 polymorphism on cytokine response in healthy children
2008 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, Vol. 68, no 3, 345-350 p.Article in journal (Refereed) Published
Type 1 diabetes (T1D) is considered to be a T-cell-mediated autoimmune disease in which genetic predisposition is affected by HLA class II alleles and polymorphisms in cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene. We tested the hypothesis whether these T1D-related gene polymorphisms modulate cytokine response and thus contribute to the development of autoimmunity. The study includes 67 non-diabetic children, typed for HLA class II alleles and CTLA-4 polymorphisms (+49A/G, CT60A/G, CTBC217_1C/T). We measured cytokine secretion of peripheral blood mononuclear cells after stimulation with tetanus toxoid (TT), polio virus, coxsackie virus B4, pertussis toxin (PT) and phytohemagglutinin (PHA). We saw higher IL-13 response to TT in individuals with DR3–DQ2 haplotype (P = 0.002). HLA class II protective haplotype, DR2–DQ6, showed association with increased production of IFN-γ (P < 0.001) and IL-2 (P = 0.005) in response to polio virus. In children with the autoimmunity-related homozygous genotypes CTLA-4 +49G/G, CT60G/G and CTBC217_1T/T, we found enhanced PT- and PHA-induced IFN-γ production (P < 0.05). The cytokine responses to studied antigens were weakly modified by HLA class II risk haplotypes, and children with T1D-associated HLA risk haplotypes are not specifically inclined to develop an immune response in general. Higher IFN-γ and IL-2 response to enterovirus in children with HLA class II protective haplotype DR2-DQ6 could be of importance in the protection from T1D-associated enterovirus infections. All autoimmunity related CTLA-4 polymorphisms were associated with enhanced IFN-γ. This suggests impaired downregulation of cellular immunity by these CTLA-4 polymorphisms.
Place, publisher, year, edition, pages
2008. Vol. 68, no 3, 345-350 p.
IdentifiersURN: urn:nbn:se:liu:diva-12436DOI: 10.1111/j.1365-3083.2008.02144.xOAI: oai:DiVA.org:liu-12436DiVA: diva2:75