Kukko Marika, Toivonen Anna, Kupila Antti, Korhonen Sari, Keskinen Päivi, Veijola Riitta, Virtanen Suvi M, Ilonen Jorma, Simell Olli, Knip Mikael
JDRF Centre for the Prevention of Type 1 Diabetes in Finland.
Diabetes Metab Res Rev. 2006 Jan-Feb;22(1):53-8. doi: 10.1002/dmrr.584.
Type 1 diabetes is characterised by familial aggregation. We set out to explore whether beta-cell autoimmunity, which is considered to precede clinical disease, also shows familial clustering.
Tests for HLA DQB1 alleles (*02, *0301, *0302, *0602) and islet cell autoantibodies (ICA) were performed on 5836 children from 2283 families. When a child tested positive for ICA, all his/her previous or subsequent samples that were available were also tested for insulin autoantibodies (IAA), antibodies to glutamic acid decarboxylase (GADA) and antibodies to the IA-2 protein (IA-2A).
Forty-four families were observed to have two or more children positive for at least ICA. This proportion (1.9%) was almost five times higher than expected (0.4%; p < 0.001). The frequency of multiple (>/=2) autoantibodies also showed familial aggregation, the observed proportion (0.39%) being three times that expected (0.13%; p < 0.001). In 72.7% of the families with at least two ICA-positive siblings, the children with autoantibodies had the same HLA DQB1 genotype. The median age difference between the ICA-positive children within the same family was 3.3 years (range 0.0-10.5 years), and the median time interval in the appearance of ICA within the family was 1.6 years (range 0.0-3.2).
beta-cell autoimmunity, as defined by the appearance of ICA, demonstrates familial aggregation, although the antibodies do not appear in close temporal proximity or at an identical age within the same family. The HLA-DQB1 genotypes are more often identical in siblings with autoantibodies than in other siblings.
1型糖尿病具有家族聚集性。我们旨在探究被认为先于临床疾病出现的β细胞自身免疫是否也存在家族聚集现象。
对来自2283个家庭的5836名儿童进行了HLA DQB1等位基因（*02、*0301、*0302、*0602）和胰岛细胞自身抗体（ICA）检测。当一名儿童ICA检测呈阳性时，其所有可用的先前或后续样本也会进行胰岛素自身抗体（IAA）、谷氨酸脱羧酶抗体（GADA）和IA-2蛋白抗体（IA-2A）检测。
观察到44个家庭中有两个或更多儿童至少ICA检测呈阳性。这一比例（1.9%）几乎是预期比例（0.4%；p<0.001）的五倍。多种（≥2种）自身抗体的频率也显示出家族聚集性，观察到的比例（0.39%）是预期比例（0.13%；p<0.001）的三倍。在至少有两名ICA阳性兄弟姐妹的家庭中，72.7%的有自身抗体的儿童具有相同的HLA DQB1基因型。同一家族中ICA阳性儿童的年龄中位数差异为3.3岁（范围0.0 - 10.5岁），家族中ICA出现的时间间隔中位数为1.6年（范围0.0 - 3.2年）。
由ICA出现所定义的β细胞自身免疫表现出家族聚集性，尽管在同一家族中抗体并非在相近时间出现或年龄相同。有自身抗体的兄弟姐妹的HLA - DQB1基因型比其他兄弟姐妹更常相同。
