Sarugeri E, Dozio N, Belloni C, Meschi F, Pastore M R, Bonifacio E
Departments of Internal Medicine, Instituto Scientifico San Raffaele, Milan, Italy.
Clin Exp Immunol. 1998 Dec;114(3):370-6. doi: 10.1046/j.1365-2249.1998.00744.x.
Type 1 diabetes is associated with autoimmunity to insulin. Genetic susceptibility to type 1 diabetes is polygenic and includes the INS VNTR-IDDM2 locus which may regulate the expression of insulin in pancreas and thymus. In order to determine whether insulin autoimmunity could be attributed to a genetic susceptibility conferred by the INS VNTR-IDDM2 locus, peripheral blood T cell proliferation to human insulin and insulin autoantibodies (IAA) was measured in patients with new onset type 1 diabetes and control subjects. IAA were detected in 21 of 53 patients and in none of 25 control subjects, while T cell responses were low (stimulation index range 0.4-7.2) and similar in both groups. Both antibody and T cell responses were higher in younger subjects and IAA were more prevalent in patients with the HLA-DR4 allele. No relationship was observed between humoral and cellular responses to insulin. No association was found between the INS VNTR-IDDM2-susceptible allele and insulin autoimmunity. Increased T cell responses and IAA were found in patients with either the diabetes-susceptible or the diabetes-protective INS VNTR-IDDM2 locus genotypes, and increased T cell responses were also found in control subjects with either susceptible or protective INS VNTR-IDDM2 locus genotypes. This study confirms that primary T cell proliferative responses to insulin are low and detectable also in control subjects. The detection of T cell proliferation and autoantibodies to insulin in subjects with and without the protective INS VNTR-IDDM2 locus genotypes does not support the hypothesis of an allele-specific capacity for tolerance induction which could determine a susceptibility to develop autoimmunity against the insulin protein and subsequently diabetes.
1型糖尿病与针对胰岛素的自身免疫有关。1型糖尿病的遗传易感性是多基因的，包括INS VNTR-IDDM2位点，该位点可能调节胰岛素在胰腺和胸腺中的表达。为了确定胰岛素自身免疫是否可归因于INS VNTR-IDDM2位点赋予的遗传易感性，对新诊断的1型糖尿病患者和对照受试者测量了外周血T细胞对人胰岛素和胰岛素自身抗体（IAA）的增殖反应。53例患者中有21例检测到IAA，25例对照受试者均未检测到，而两组的T细胞反应均较低（刺激指数范围为0.4-7.2）且相似。年轻受试者的抗体和T细胞反应均较高，IAA在携带HLA-DR4等位基因的患者中更为普遍。未观察到对胰岛素的体液和细胞反应之间存在关联。未发现INS VNTR-IDDM2易感等位基因与胰岛素自身免疫之间存在关联。在具有糖尿病易感或糖尿病保护INS VNTR-IDDM2位点基因型的患者中均发现T细胞反应增加和IAA增加，在具有易感或保护INS VNTR-IDDM2位点基因型的对照受试者中也发现T细胞反应增加。本研究证实，对照受试者中对胰岛素的原发性T细胞增殖反应较低且可检测到。在具有和不具有保护性INS VNTR-IDDM2位点基因型的受试者中检测到T细胞增殖和胰岛素自身抗体，不支持等位基因特异性耐受诱导能力的假设，该假设可能决定对胰岛素蛋白产生自身免疫并随后发生糖尿病的易感性。
