Children's Hospital, University of Helsinki and Helsinki University Central Hospital, PO Box 22, FI-00014 Helsinki, Finland.
Eur J Endocrinol. 2013 Jun 29;169(2):171-8. doi: 10.1530/EJE-13-0089. Print 2013 Aug.
Based on the concept of clustering autoimmunity, children with a positive family history of autoimmunity could be expected to have a different pathogenetic form of type 1 diabetes (T1D) and thus a stronger autoimmune reactivity against β-cells and an increased prevalence of the HLA-DR3-DQ2 haplotype.
We tested this hypothesis in a cross-sectional observational study from the Finnish Pediatric Diabetes Register. HLA class II genotypes and β-cell autoantibodies were analyzed, and data on the extended family history of autoimmunity and clinical markers at diagnosis were collected with a structured questionnaire from 1488 children diagnosed with T1D under the age of 15 years (57% males).
Only 23 children (1.5%) had another autoimmune disease (AID) known at diagnosis, and they had a milder metabolic decompensation at diabetes presentation. One-third (31.4%) had at least one relative with an AID other than T1D with affected mothers being overrepresented (8.2%) compared with fathers (2.8%). The children with a positive family history of other AIDs had higher levels of islet cell antibodies (P=0.003), and the HLA-DR3-DQ2 haplotype in the children was associated with celiac disease in the extended family (P<0.001), but not with an increased frequency of autoimmune disorders, in general.
Approximately one-third of children with newly diagnosed T1D have a first- and/or second-degree relative affected by an AID. Our data do not consistently support the hypothesis of differential pathogenetic mechanisms in such children.
基于聚类自身免疫的概念，自身免疫阳性家族史的儿童可能具有不同的 1 型糖尿病（T1D）发病形式，因此对β细胞的自身免疫反应更强，HLA-DR3-DQ2 单倍型的患病率更高。
我们在芬兰儿科糖尿病登记处的一项横断面观察性研究中检验了这一假设。分析了 HLA Ⅱ类基因型和β细胞自身抗体，并通过结构化问卷从 1488 名 15 岁以下确诊为 T1D 的儿童（男性占 57%）收集了有关自身免疫扩展家族史和诊断时临床标志物的数据。
只有 23 名儿童（1.5%）在诊断时患有另一种已知的自身免疫性疾病（AID），且在发病时代谢失代偿程度较轻。三分之一（31.4%）至少有一位亲属患有除 T1D 以外的 AID，受影响的母亲占比（8.2%）明显高于父亲（2.8%）。有阳性家族史的其他自身免疫性疾病的儿童胰岛细胞抗体水平更高（P=0.003），且 HLA-DR3-DQ2 单倍型与扩展家族中的乳糜泻相关（P<0.001），但与一般自身免疫性疾病的发生率增加无关。
大约三分之一新诊断的 T1D 儿童有一级和/或二级亲属患有 AID。我们的数据并不一致支持此类儿童存在不同发病机制的假设。
