EARLY MOLECULAR AND IMMUNE MARKERS AS A BASIS FOR DIFFERENTIATED THERAPY OF TYPE 2 AUTOIMMUNE POLYGLANDULAR SYNDROME (LITERATURE REVIEW)
Keywords:
type 2 autoimmune polyglandular syndrome, autoantibodies, targeted therapy, immunomodulation, personalized medicineAbstract
Type 2 autoimmune polyglandular syndrome (APS-2) is a complex endocrine disorder characterized by a combination of autoimmune pathologies, such as Addison’s disease, autoimmune thyroiditis, and type 1 diabetes mellitus. Despite significant progress in the study of APS-2, its pathogenesis, diagnosis, and therapy remain relevant research areas. This literature review examines modern molecular and immune markers that play a key role in the early detection and prognosis of the disease. Genetic predispositions, including HLA-DR3 and HLA-DR4 alleles, as well as polymorphisms in the CTLA-4, PTPN22, FOXP3, and STAT4 genes, are analyzed. Special attention is paid to epigenetic factors such as DNA methylation and the influence of non-coding RNAs on immune mechanisms. Key immune markers, including autoantibodies to 21-hydroxylase, GAD65, and IA-2, as well as the role of pro-inflammatory cytokines and changes in the T-lymphocyte population, are considered. The review highlights prospects for differentiated therapy, including targeted monoclonal antibodies, antigen-specific immunotherapy, cellular technologies, and metabolic regulation. Further research into APS-2 mechanisms will contribute to the improvement of diagnostic and therapeutic approaches, enhancing the effectiveness of personalized medicine in endocrinology.
References
Barker J.M., Yu L., Eisenbarth G.S. Autoantibodies in diabetes. Diabetes Care. 2019;42(5):869-876.
Betterle C., Dal Pra C., Mantero F., Zanchetta R. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: New insights. Journal of Endocrinological Investigation. 2018;41(8):865-875.
Dendrou C.A., Petersen J., Rossjohn J. Role of CD25 in autoimmune diseases: A new insight. Trends in Immunology. 2023;44(2):124-136.
Gianchecchi E., Fierabracci A. Insights into the role of epigenetics in autoimmune diseases. Frontiers in Immunology. 2022;13:875212.
Gonzalez F.J., Strowig T., Flavell R.A. Peptide-based immunotherapy for autoimmune diseases. Nature Reviews Drug Discovery. 2023;22(1):34-50.
Husebye E.S., Anderson M.S., Kampe O. Autoimmune polyendocrine syndromes. The New England Journal of Medicine. 2020;382(12):1133-1144.
Husebye E.S., Perheentupa J., Rautemaa R. Autoimmune polyendocrinopathy syndromes and immune deficiency. Endocrine Reviews. 2022;43(3):467-492.
Johnson M.B., Kawakami T., Takahashi Y. IL-2 receptor and immune regulation in endocrine autoimmunity. Cellular & Molecular Immunology. 2021;18(5):1156-1165.
Kahles H.K., Heinig B., Mandrup-Poulsen T. CTLA-4 and its role in autoimmune endocrine diseases. Nature Reviews Endocrinology. 2019;15(2):89-103.
Kahles H.K., Peters B., Mandrup-Poulsen T. Autoimmune endocrine diseases and checkpoint inhibitors. Trends in Endocrinology & Metabolism. 2023;34(2):89-102.
Kawasaki E., Eguchi K. Molecular and genetic bases of type 1 diabetes in Japanese population. Journal of Diabetes Investigation. 2022;13(4):735-748.
Myers P., Gianchecchi E., Fierabracci A. Genetic and epigenetic patterns in autoimmune polyendocrine syndromes. Frontiers in Endocrinology. 2021;12:647632.
Simmonds M.J., Gough S.C.L. The role of viral infections in autoimmune disease. Current Opinion in Immunology. 2021;73:10-16.
Smith A.G., Clark P., Li X. Epigenetic modifications in autoimmunity: New insights. Frontiers in Genetics. 2022;13:765987.
Wang L., Zhang H., Xiao X. Role of TET2 in immune tolerance and autoimmunity. Immunological Reviews. 2023;310(1):72-87.
Wang X., Chen J., Xu Y. Regulatory T cell therapy in autoimmune endocrine diseases. Immunotherapy. 2023;15(2):97-112.
Wu C., Yu X., Liu J. The metabolic pathways in autoimmune endocrinopathies. Metabolism. 2023;140:155347.
Wu H., Esteve E., Tremaroli V. The gut microbiota in endocrine disorders. Nature Reviews Endocrinology. 2023;19(3):151-167.
Wu H.J., Ivanov I.I., Darce J. Gut microbiota and systemic autoimmunity. Immunity. 2023;58(6):1065-1079.
Zhang J., Liu Y., Zhao X. MicroRNA regulation in autoimmune diseases: A new therapeutic strategy? Autoimmunity Reviews. 2023;22(5):102713.
Zhang L., Feng Y., Lu Y. PD-1 blockade therapy and its impact on autoimmune endocrinopathies. Clinical Endocrinology. 2022;97(4):488-497.
Zhang Q., Wang Y., Zhu L. Autoantibodies in autoimmune polyglandular syndromes: Pathogenic significance. Journal of Autoimmunity. 2023;135:102989.
Zhao W., Li J., Wang S. Role of pro-inflammatory cytokines in autoimmune endocrine diseases. Journal of Clinical Immunology. 2022;42(4):765-779.
