Stability of autoantibodies and their relation to genetic and metabolic markers of Type I diabetes in initially unaffected schoolchildren
Stability of autoantibodies and their relation to genetic and metabolic markers of Type I diabetes in initially unaffected schoolchildren
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DOI：
10.1007/s001250051329
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发表时间：
2000-04-01
期刊：
影响因子：
8.2
通讯作者：
Knip, M
中科院分区：
文献类型：
--
作者：
Kulmala, P;Rahko, J;Knip, M
目的/假设。研究非糖尿病学龄儿童中与I型（胰岛素依赖型）糖尿病相关的自身抗体阳性率的时间变化以及这些抗体、HLA-DQB1风险标志物和第一时相胰岛素反应（FPIR）之间的关系。在104名最初对胰岛细胞抗体（ICA）或谷氨酸脱羧酶（GADA）65 000 M-r亚型抗体呈阳性或两者均呈阳性的学童以及104名抗体阴性对照儿童中评估了2年内抗体状态的稳定性。性别、年龄和居住地。所有儿童在第二次随访时也进行了第一时相胰岛素反应和HLA-DQB 1等位基因的研究。第二次，98名最初ICA阳性儿童中有3名，IA-2蛋白抗体（IA-2A）阳性儿童中有3/13名，GADA阳性儿童中有1/17名，胰岛素自身抗体（IAA）阳性儿童中有2/7名，这些抗体检测为阴性。IA-2A，GADA，IAA和多种（2 2）抗体的儿童有显着低于对照组儿童的第一时相胰岛素反应。与此相反，这些反应没有不同的受试者和没有特定的HLA-DQB 1风险等位基因或基因型。在第一时相胰岛素反应显著降低的六名受试者中，三名在两种情况下都有多种抗体，但他们中没有一人具有DQB 1基因型，从而增加糖尿病风险。两名受试者在3.4年的随访中进展为I型糖尿病，他们都有多种抗体和显著降低的第一时相胰岛素反应，但他们都没有DQB 1风险基因型。糖尿病相关自身抗体阳性在未受影响的学龄儿童中是一种相对稳定的现象，尽管偶尔会发生血清阴性的转化。我们的观察还表明，与I型糖尿病易感性降低相关的DQB1等位基因不能保护最初未受影响的学龄儿童免受β细胞功能受损或进展为明显疾病。
Aims/hypothesis. To study temporal changes in positivity for autoantibodies associated with Type I (insulin-dependent) diabetes mellitus and the relations between these antibodies, HLA-DQB1-risk markers and first-phase insulin response (FPIR) in non-diabetic schoolchildren.Methods. The stability of the antibody status over 2 years was assessed in 104 schoolchildren initially positive for islet cell antibodies (ICA) or antibodies to the 65 000 M-r isoform of the glutamic acid decarboxylase (GADA) or both and in 104 antibody-negative control children matched for sex, age and place of residence. All children were also studied for their first-phase insulin response and HLA-DQB1 alleles on the second occasion.Results. On the second occasion 3 of the 98 initially ICA-positive children, 3/13 of those positive for antibodies to the IA-2 protein (IA-2A), 1/17 GADA-positive and 2/7 of those positive for insulin autoantibodies (IAA) tested negative for these antibodies. Children with IA-2A, GADA, IAA and multiple (2 2) antibodies had significantly lower first-phase insulin responses than the control children. In contrast, these responses did not differ between subjects with and without specific HLA-DQB1-risk alleles or genotypes. Of the six subjects with a considerably reduced first-phase insulin response three had multiple antibodies on both occasions but none of them had a DQB1 genotype conferring increased diabetes risk. Two subjects progressed to Type I diabetes within 3.4 years of follow-up, both of them having multiple antibodies and a considerably reduced first-phase insulin response but neither of them having a DQB1-risk genotype.Conclusions/interpretation. Positivity for diabetes-associated autoantibodies is a relatively stable phenomenon in unaffected schoolchildren, although conversion to seronegativity can occur occasionally. Our observations also indicate that DQB1 alleles associated with decreased susceptibility to Type I diabetes do not protect from impaired beta-cell function or from progression to overt disease in initially unaffected schoolchildren.