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Electrochemiluminescence Assays for Human Islet Autoantibodies
Published on: March 23, 2018
Dynamics of Islet Autoantibodies During Prospective Follow-Up From Birth to Age 15 Years
Petra M Pöllänen1,2, Samppa J Ryhänen1, Jorma Toppari3
1Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Insights
In children genetically predisposed to type 1 diabetes (T1D), the type of islet autoantibody that appears first changes with age. Autoantibody persistence influences T1D progression, aiding prediction and prevention strategies.
Area of Science:
- Immunology
- Endocrinology
- Pediatrics
Background:
- Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic beta cells.
- Genetic predisposition plays a significant role in T1D development.
- Understanding the dynamics of islet autoantibodies is crucial for early detection and prevention.
Purpose of the Study:
- To characterize the temporal dynamics of islet autoantibodies in genetically susceptible children over 15 years.
- To investigate the role of zinc transporter 8 autoantibodies (ZnT8A) in the natural history of T1D autoimmunity.
- To identify patterns of autoantibody seroconversion and their association with T1D onset.
Main Methods:
- Longitudinal observation of 1006 HLA-predisposed children from birth up to 15.5 years.
- Systematic assessment of multiple islet autoantibodies including ZnT8A, islet cell (ICA), insulin (IAA), glutamate decarboxylase (GADA), and islet antigen-2 (IA-2A).
- Monitoring for progression to T1D.
Main Results:
- 3.5% of children developed T1D by age 15.5.
- Islet autoimmunity occurred in 27.3% of children, with a median age of 7.4 years at seroconversion.
- Autoantibody profiles varied by age: ZnT8A and IAA were common early, while IA-2A and GADA increased later; GADA persisted until age 15.
- Inverse IAA seroconversions were frequent and associated with a longer delay to diagnosis.
Conclusions:
- The primary autoantibody in genetically predisposed children is age-dependent, potentially reflecting distinct disease-driving events.
- Autoantibody persistence is a key factor influencing T1D risk.
- These findings support personalized approaches to T1D prediction and prevention by identifying distinct disease subpopulations.
Context:
We set out to characterize the dynamics of islet autoantibodies over the first 15 years of life in children carrying genetic susceptibility to type 1 diabetes (T1D). We also assessed systematically the role of zinc transporter 8 autoantibodies (ZnT8A) in this context.
Design:
HLA-predisposed children (N = 1006, 53.0% boys) recruited from the general population during 1994 to 1997 were observed from birth over a median time of 14.9 years (range, 1.9-15.5 years) for ZnT8A, islet cell (ICA), insulin (IAA), glutamate decarboxylase (GADA), and islet antigen-2 (IA-2A) antibodies, and for T1D.
Results:
By age 15.5 years, 35 (3.5%) children had progressed to T1D. Islet autoimmunity developed in 275 (27.3%) children at a median age of 7.4 years (range, 0.3-15.1 years). The ICA seroconversion rate increased toward puberty, but the biochemically defined autoantibodies peaked at a young age. Before age 2 years, ZnT8A and IAA appeared commonly as the first autoantibody, but in the preschool years IA-2A- and especially GADA-initiated autoimmunity increased. Thereafter, GADA-positive seroconversions continued to appear steadily until ages 10 to 15 years. Inverse IAA seroconversions occurred frequently (49.3% turned negative) and marked a prolonged delay from seroconversion to diagnosis compared to persistent IAA (8.2 vs 3.4 years; P = .01).
Conclusions:
In HLA-predisposed children, the primary autoantibody is characteristic of age and might reflect the events driving the disease process toward clinical T1D. Autoantibody persistence affects the risk of T1D. These findings provide a framework for identifying disease subpopulations and for personalizing the efforts to predict and prevent T1D.
