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 b-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 b-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 (PZ0.003), 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.

Increased circulating concentrations of mesencephalic astrocyte-derived neurotrophic factor in children with type 1 diabetes

“…All study subjects were derived from the Finnish Pediatric Diabetes Register and Sample Repository 38 . Parents or legal guardians of children under 18 years of age participating the study and all study subjects aged 18 years or above gave written informed consent.…”

“…We thank the Finnish Pediatric Diabetes Register for making the serum samples available for this study. The members of the Register are listed in the acknowledgements of reference 38 . This study was supported by the Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research 2012–2017, Centre of Excellence in Molecular and Integrated Neuroscience Research 2008–2013, and Grant No.…”

Coexisting psoriasis affects the clinical course of type 1 diabetes in children

“…T1D and childhood psoriasis share similar ages of onset, around 8 for T1D [11] and 8-10 for psoriasis, according to various reports [12,13]. Importantly, in both diseases positive familial history is consistently reported.…”

“…Importantly, in both diseases positive familial history is consistently reported. In children with T1D, 12.2% have an affected first-degree relative and 21.8% a first or second-degree relative [11]. In patients with psoriasis familial component is even more pronounced with 13.6% to 71% of children with an affected first-degree family member in different population studies [9,12,14].…”

Celiac disease as an autoimmune condition

“…One or more CD HLA-DQ heterodimers increased the risk of developing CD ( p < 0.001) [ 42 ]. The HLA-DR3-DQ2 haplotype in children with T1DM was associated with CD in the extended family ( p < 0.001) [ 43 ]. By stratifying the HLADQ, Östensson et al .…”