Extended family history of autoimmune diseases and phenotype and genotype of children with newly diagnosed type 1 diabetes

Abstract

Objective: 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.

Design and methods: 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).

Results: 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.

Conclusions: 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.