Content of Diabetes-Associated Autoantibodies against Islet Autoantigens (IA-2A, GADA, IAA) and the Level of Different Cytokines in Children and Adolescents on the Pre-Clinical and Early Clinical Stages of Type 1 Diabetes Mellitus Development

V.V. Popova

Abstract


The article provides the data on the immunological mechanisms of type 1 diabetes mellitus (T1DM) on the preclinical and early clinical stages of disease formation on the basis of studying the features of T1DM pathogenesis, monitoring the process of autoimmune destruction of insulin-producing β-cells by determining the content of diabetes-associated auto-antibodies (the incidence and titers dynamics), the study of the characteristics of cytokine secretion on the pre-clinical stage of T1DM development in children and adolescents. Introduction of new approaches to pre-clinical diagnosis of T1DM allowed determine the group of marker-positive children with burdened heredity and predictable risk of disease development. The study involved 450 healthy normoglycemic children and adolescents aged from 7 to 15 years old. It was revealed that 94 (26.7 %) of 366 children with burdened hereditary by at least two-fold determination of DAAb had an increased DAAb titer, mainly GADA and IA-2A, the clinical debut of T1DM manifested in 49 (52.1 %) of them from 6 months to 12 years (30.9 ± 3.2 months). T1DM developed in the same period in a child, that was 0.8 % of the 272 (73.3 %) DAAb-negative children. There was determined a formula of combined incidence and values of simultaneously elevated DAAb titers to islet autoantigens, namely IA-2A + GADA, which are predictor of the duration of T1DM pre-clinical stage and debut occurrence. It has been also established a disturbance of cytokine production (increased level of pro-inflammatory cytokines IL-1α, IL-6 and FNO-α, IL-8 and IL-16 while reduced concentration of IL-4 in blood plasma) as a key factor in the T1DM pathogenesis that causes the debut occurrence, and aggressiveness of its course.


Keywords


type 1 diabetes mellitus; children and adolescents; diabetes-associated auto-antibodies; auto-antibodies to glutamic acid decarboxylase; auto-antibodies to tyrosine phosphatase protein (IA-2A); cytokines IL-1α; IL-4; IL-6; TNF-α; IFN-γ; IL-8 and IL-16

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DOI: https://doi.org/10.22141/2224-0721.2.66.2015.75454

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