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Updated: May 9, 2025
Electrochemiluminescence Assays for Human Islet Autoantibodies
Published on: March 23, 2018
Extremely Early Appearance of Islet Autoantibodies in Genetically Susceptible Children
Anni Kyrönniemi1,2, Toni Valtanen1,2, Jaakko Koskenniemi3,4
1Department of Pediatrics, Research Unit of Clinical Medicine, Medical Research Center, University of Oulu, P.O. Box 5000, Oulu 90014, Finland.
Insights
Extremely early islet autoimmunity in children is rare, often starting with insulin autoantibodies (IAA). This early autoimmunity has decreased over time in recent birth cohorts.
Area of Science:
- Pediatrics
- Immunology
- Endocrinology
Background:
- Type 1 diabetes (T1D) is an autoimmune disease characterized by islet autoantibodies.
- Early detection of islet autoimmunity in genetically at-risk children is crucial for understanding T1D development.
- The incidence of T1D and its preceding autoimmunity has shown temporal changes.
Purpose of the Study:
- To investigate the characteristics of islet autoantibodies appearing by 0.50 years of age in at-risk children.
- To examine differences in early islet autoimmunity across four birth cohorts (1994-2019) in Finland.
- To correlate early autoimmunity with the incidence of Type 1 diabetes (T1D).
Main Methods:
- Analysis of data from the Finnish DIPP and TEDDY studies.
- Inclusion of children with HLA-conferred T1D risk, monitored for islet autoantibodies.
- Exclusion of maternally transferred antibodies using cord, child, and maternal serum samples.
Main Results:
- Among 20,979 children, 0.25% developed islet autoantibodies by 0.50 years; 15.1% of these progressed to T1D.
- Insulin autoantibodies (IAA) were the most common initial autoantibody; IAA-initiated autoimmunity led to earlier T1D diagnosis than ZnT8A-initiated autoimmunity.
- Appearance of islet autoantibodies by 0.50 years decreased across birth cohorts from 1994-2019 (p=0.016).
Conclusions:
- Islet autoimmunity by 0.50 years is uncommon in susceptible children, typically initiated by IAA.
- Confirmed islet autoimmunity was less frequent in children with autoantibodies at ≤0.50 years compared to those with autoantibodies at 0.51-0.75 years.
- A secular decrease in early-onset islet autoimmunity (before 0.50 years) was observed in recent Finnish birth cohorts.
Objective:
We studied the characteristics of children who developed islet autoantibodies by the age of 0.50 years and hypothesized that the appearance of extremely early islet autoimmunity differs between four birth cohorts within 1994-2019 according to the change in the incidence of Type 1 diabetes (T1D) in Finland.
Methods:
Data from Finnish children participating in the Type 1 Diabetes Prediction and Prevention (DIPP) study, or the Environmental Determinants of Diabetes in the Young (TEDDY) study were analyzed. These studies follow children with increased HLA-conferred risk for T1D with regular measurements of islet autoantibodies. Maternally transferred antibodies were excluded by comparing islet autoantibodies in cord serum, child's first follow-up serum and the maternal serum.
Results:
Among 20,979 Finnish children at increased risk to T1D, 53 (0.25%) developed at least one islet autoantibody at the age of ≤0.50 years. During a mean follow-up of 8.1 years, 15.1% progressed to T1D (median age at diagnosis 2.0 years), 43.4% developed confirmed islet autoimmunity but no T1D, and 41.5% had only transient islet autoantibodies. IAA was the most common first-appearing autoantibody. Among progressors, age at diagnosis was 1.0-2.4 years in children with IAA-initiated autoimmunity and 4.5-16.1 years in ZnT8A-initiated autoimmunity. When comparing children developing autoantibodies either at the age of ≤0.50 years or 0.51-0.75 years, confirmed positivity during follow-up was more common in the older group (81.7% vs. 58.5%; p=0.002). In four birth cohorts within 1994-2019 appearance of islet autoantibodies at the age of ≤0.50 years decreased towards the most recent birth cohorts (p=0.016).
Conclusion:
Islet autoimmunity by the age of 0.50 years was rare in genetically susceptible children and was typically initiated with IAA. Confirmed positivity was less common in children with autoantibodies at age ≤0.50 than at slightly older age. The secular decrease of islet autoimmunity before age 0.50 years was observed. This trial is registered with NCT03269084 and NCT00279318.
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