Role of insulin autoantibody affinity as a predictive marker for type 1 diabetes in young children with HLA-conferred disease susceptibility

• Published in: Diabetes/metabolism research and reviews 2009-10, Vol.25 (7), p.615-622
• Main Authors: Siljander, Heli, Härkönen, Taina, Hermann, Robert, Simell, Satu, Hekkala, Anne, Salonsaari, Riikka-Tiina, Simell, Tuula, Simell, Olli, Ilonen, Jorma, Veijola, Riitta, Knip, Mikael
• Format: Article
• Language: English
• Subjects: affinity; Age Factors; Antibody Affinity; Autoantibodies - blood; Autoantibodies - immunology; Biological and medical sciences; Biomarkers - blood; Child; Child, Preschool; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Disease Progression; Disease Susceptibility; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Finland; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; General aspects; general population; genetic susceptibility; Glutamate Decarboxylase - immunology; HLA Antigens - genetics; HLA Antigens - immunology; Humans; Infant; Insulin Antibodies - blood; Insulin Antibodies - immunology; insulin autoantibodies; Matched-Pair Analysis; Medical sciences; Prediabetic State - blood; Prediabetic State - immunology; prediction; Predictive Value of Tests; Receptor-Like Protein Tyrosine Phosphatases, Class 8 - immunology; Retrospective Studies; type 1 diabetes; Vertebrates: endocrinology
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.998

Background Insulin autoantibodies (IAA) are early markers of prediabetic autoimmunity. As transient and fluctuating IAA positivity are common among young children, distinguishing non‐progressive IAA from destruction‐related IAA is essential when preventive measures are considered. We tested whether children progressing rapidly to type 1 diabetes (progressors) are characterized by a higher prediabetic IAA affinity than IAA‐positive children remaining unaffected or progressing more slowly to diabetes (non‐progressors), and whether IAA affinity increases towards diagnosis. Methods Finnish children with HLA‐conferred diabetes susceptibility were observed from birth for diabetes‐associated autoantibodies and progression to overt type 1 diabetes. IAA levels and affinities of the first IAA‐positive prediabetic samples and samples obtained closest to the diagnosis in 64 progressors were compared with corresponding values in 64 matched IAA‐positive non‐progressors. Results The median age at diagnosis was 3.9 years in progressors and the median follow‐up time 7.6 years among unaffected subjects. In the first samples the median IAA affinity was 1.4 × 1010 L/mol in both groups (p = 0.33), while at the second sampling it was 1.1 × 1010 L/mol in progressors and 1.2 × 1010 L/mol in unaffected subjects (p = 0.46). No changes in affinity levels were observed (p = 0.33 and p = 0.84, respectively). IAA titers increased towards diagnosis among progressors (from a median of 13.6 to 20.1 relative units; p = 0.02). Conclusions Among young IAA‐positive children with HLA‐conferred disease susceptibility IAA affinity failed to distinguish rapid progressors from slowly or non‐progressing subjects. In relation to IAA affinity, no maturation of the humoral immune response was observed over time from seroconversion to diagnosis. Copyright © 2009 John Wiley & Sons, Ltd.