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. 2020 Dec 1;105(12):e4638-e4651.
doi: 10.1210/clinem/dgaa624.

Dynamics of Islet Autoantibodies During Prospective Follow-Up From Birth to Age 15 Years

Petra M Pöllänen  1   2 , Samppa J Ryhänen  1 , Jorma Toppari  3 , Jorma Ilonen  4 , Paula Vähäsalo  5 , Riitta Veijola  5 , Heli Siljander  1   2 , Mikael Knip  1   2   6   7
Affiliations

Dynamics of Islet Autoantibodies During Prospective Follow-Up From Birth to Age 15 Years

Petra M Pöllänen et al. J Clin Endocrinol Metab. .

Abstract

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.

Keywords: HLA; children; dynamics; islet autoantibodies; prediction; type 1 diabetes.

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Figures

Figure 1.
Figure 1.
Development of islet cell (ICA), insulin (IAA), glutamate decarboxylase (GADA), islet antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) antibodies by age 15.5 years.
Figure 2.
Figure 2.
Autoantibodies at initial seroconversion among progressors and nonprogressors. *P less than .001. **P less than .002.
Figure 3.
Figure 3.
Autoantibody profiles at initial seroconversion in the age groups 0 to 2 (N = 41), 2 to 5 (N = 51), 5 to 10 (N = 97), and 10 to 15.5 (N = 86) years. *P less than .05 compared to all other groups. †P less than .05 0 to 2 vs 2 to 5, 0 to 2 vs 5 to 10, 0 to 2 vs 10 to 15.5, 2 to 5 vs 5 to 10, 2 to 5 vs 10 to 15.5 years. ‡P less than .05 0 to 2 vs 2 to 5, 0 to 2 vs 5 to 10, 0 to 2 vs 10 to 15.5, 2 to 5 vs 5 to 10 years. §P less than .05 0 to 2 vs 5 to 10, 0 to 2 vs 10 to 15.5 years.
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