Assessment of the risk of developing autoimmune polyglandular syndrome type 3a in children with type 1 diabetes

Objective. To develop a prognostic model for determining the probability of autoimmune polyglandular syndrome type 3a development in children with type 1 diabetes.

Materials and methods. A comparative analysis of the data of 52 children with autoimmune polyglandular syndrome type 3a, 95 patients with type 1 diabetes, and 30 healthy children was performed. The analyzed data included: anamnesis, levels of diabetes-associated antibodies (against tyrosine phosphatase, insulin, glutamate decarboxylase, zinc transporter 8), polymorphic variants of genes (CTLA-4, PTPN22, HLA-DRB1, -DQB1, -DQA1).

Results. Factors associated with thyroid autoimmunity in children with type 1 diabetes were identified: onset of diabetes at the age < 3 or > 12 (girls)/13 (boys) years (OR = 2.84, 95 % CI (1.30–6.20)), family history of autoimmune thyroid diseases (OR = 3.14, 95 % CI (1.33–6.55)); levels of zinc transporter 8 antibodies > 460.0 IU/mL with diabetes duration less than 3 years and levels of glutamate decarboxylase antibodies > 43.0 IU/mL with disease duration more than 3 years (OR = 5.48, 95 % CI (2.52–11.88)); combined genotypes: in girls – rs231775 CTLA-4_AG+GG/rs2476601 PTPN22_СT+TT; in boys – rs231775 CTLA-4_AG+GG/HLA-DRB1*04:Х/04:Х (where DRB1*04: X – alleles DRB1*04:01, 04:02, 04:04, 04:05, 04:10), (OR = 5.01, 95 % CI (2.21–11.36)).

A prognostic model with 77.3 % sensitivity and 63.7 % specificity was constructed to determine the probability of developing autoimmune thyroid disease in children with type 1 diabetes. An algorithm was developed to stepwise stratify high-risk groups of autoimmune polyglandular syndrome type 3a.

Conclusion. The developed model and algorithm facilitate the individualization of autoimmune thyroid disease screening in children with type 1 diabetes.

1. Marquez A., Martin J. Genetic overlap between type 1 diabetes and other autoimmune diseases. Semin Immunopathol. 2022; 44(1): 81–97.

2. American Diabetes Association Professional Practice Committee. Children and adolescents: standards of medical care in Diabetes-2025. Diabetes Care. 2025; 48: 283–305.

3. Ogarek N., Mrowka A., Jarosz-Chobot P. Thyroid diseases – ally or enemy of type 1 diabetes in children and adolescents? Pediatr Endocrinol Diabetes Metab. 2021; 27(2): 117–122.

4. Frohlich-Reiterer Е., Elbarbary N.S., Simmons К., et al. ISPAD clinical practice consensus guidelines 2022: other complications and associated conditions in children and adolescents with type 1 diabetes. Pediatric diabetes. 2022; 23(8): 1451–1467.

5. Huang T., Li J., Zhang W. Application of principal component analysis and logistic regression model in lupus nephritis patients with clinical hypothyroidism. BMC Med Res Methodol. 2020; 20(1). Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC7195728/pdf/12874_2020_Article_989.pdf (accessed: 31.08.2025).

6. Wu J.-Y., Zhang J.-Y., Xia W.-Q., et al. Predicting autoimmune thyroiditis in primary Sjogren's syndrome patients using a random forest classifier. Arthritis Res Ther. 2025; 27(1). Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC11694358/pdf/13075_2024_Article_3469.pdf (accessed: 31.08.2025).

7. Ma Z., Cai M., Yang K., et al. Predicting the risk of autoimmune thyroid disease in patients with vitiligo: Development and assessment of a new predictive nomogram. Front Endocrinol (Lausanne). 2023; 14. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC9927026/pdf/fendo-14-1109925.pdf (accessed: 31.08.2025).

8. Volkova N.V., Solnceva A.V., Dashkevich E.I. Association of islet antiimmunity markers with autoimmune thyroid diseases in children with type 1 diabetes mellitus. Belorusskij gosudarstvennyj medicinskij universitet v avangarde medicinskoj nauki i praktiki. Minsk; 2024. (in Russian)

9. Volkova N.V., Aksenova E.A., Yackiv A.A., et al. The influence of CTLA-4 and PTPN22 gene polymorphisms in children with type 1 diabetes mellitus on the predisposition to autoimmune thyroid diseases. Molekulyarnaya i prikladnaya genetika. 2024; 36: 159–171. (in Russian)

10. Volkova N.V., Aksenova E.A., Yackiv A.A., et al. Association of HLA class II genes with autoimmune thyroid diseases in children with type 1 diabetes mellitus. Doklady Nacional'noj Akademii nauk Belarusi. 2024; 68(5): 395–403. (in Russian)

11. Volkova N.V., Aksenova E.A., Solnceva A.V., et al. Association of MICA and CTLA-4 gene polymorphisms with the risk of autoimmune thyroid diseases in children with type 1 diabetes mellitus. Izvestiya Nacional'noj akademii nauk Belarusi. Seriya medicinskih nauk. 2025; 22(4): 332–343. (in Russian)

12. Frommer L., Kahaly G.J. Type 1 diabetes and autoimmune thyroid disease-the genetic link. Front Endocrinol (Lausanne). 2021; 12. Available at: http://pmc.ncbi.nlm.nih.gov/articles/PMC7988207/pdf/fendo-12-618213.pdf (accessed: 31.08.2025).