Marttila Jane, Huttunen Suvi, Vaarala Outi, Suzuki Kunimasa, Elliott John F, Närvänen Ale, Knip Mikael, Simell Olli, Ilonen Jorma
Department of Virology, University of Turku, Turku, Finland.
J Autoimmun. 2008 Sep;31(2):142-8. doi: 10.1016/j.jaut.2008.04.024. Epub 2008 Jun 18.
Insulin-specific immune responses appear early in preclinical type 1 diabetes (T1D), and bovine insulin in cow's milk-based infant formulas has been suggested to be of importance in induction of the primary response to insulin in humans. To characterize insulin-specific T-cell reactivity we studied T-cell responses to 10 insulin peptides derived from bovine (BI) and human insulin (HI) in 42 children with recently diagnosed T1D, 47 children with multiple autoantibodies and 111 autoantibody-negative control children with risk-associated HLA alleles. Proliferation responses detected in antigen-stimulated peripheral blood mononuclear cells did not differ between the three groups when the comparison was performed without considering HLA genotypes. However, significant differences were observed, when children with the high-risk genotype HLA (DRB103)-DQA105-DQB102/DRB10401-DQA103-DQB10302 were analyzed separately. The responses to the peptides including amino acids A1-12 derived from B1 and H1 were significantly higher in children with T1D (P=0.008, P=0.004, for B1 and H1, respectively) and in children with diabetes-associated autoantibodies (P=0.002 and P=0.001, respectively) than in control children. Positive responses (stimulation indices SI> or =3) were seen more frequently in T1D children than in controls (4/7 vs 2/19; P=0.03 and 4/7 vs 1/19; P=0.01 for B1 and H1, respectively). T-cell response to the insulin peptide A1-12 is enhanced in clinical and preclinical T1D associated with the high-risk HLA-genotype emphasizing the importance of this epitope.
胰岛素特异性免疫反应在临床前1型糖尿病（T1D）早期就会出现，基于牛奶的婴儿配方奶粉中的牛胰岛素被认为在诱导人类对胰岛素的初次反应中具有重要作用。为了表征胰岛素特异性T细胞反应性，我们研究了42例新诊断的T1D儿童、47例具有多种自身抗体的儿童以及111例具有风险相关HLA等位基因的自身抗体阴性对照儿童对10种源自牛胰岛素（BI）和人胰岛素（HI）的胰岛素肽的T细胞反应。在不考虑HLA基因型进行比较时，三组在抗原刺激的外周血单核细胞中检测到的增殖反应没有差异。然而，当分别分析具有高危基因型HLA（DRB103）-DQA105-DQB102/DRB10401-DQA103-DQB10302的儿童时，观察到了显著差异。T1D儿童（分别针对B1和H1，P=0.008和P=0.004）以及患有糖尿病相关自身抗体的儿童（分别为P=0.002和P=0.001）对包括源自B1和H1的氨基酸A1-12的肽的反应显著高于对照儿童。T1D儿童中阳性反应（刺激指数SI≥3）比对照儿童更常见（分别针对B1和H1，4/7 vs 2/19；P=0.03和4/7 vs 1/19；P=0.01）。与高危HLA基因型相关的临床和临床前T1D中，T细胞对胰岛素肽A1-12的反应增强，强调了该表位的重要性。
