Functional study of cellular immunity in Brazilians with type 1 diabetes at different stages of the disease and its integration with genetic and humoral markers

Abstract

Type 1 diabetes(T1D) is one of the most common chronic diseases of childhood and adolescence, with severe prognosis if inadequately treated. There is heterogeneity in its clinical expression, depending on the extension of the destruction of pancreatic beta cells by autoreactive T lymphocytes. The presence of autoantibodies and predisposing genotype (HLA class II) allow the etiological diagnosis of the disease. An autoimmune relapsing-remitting process was proposed, involving the interference of viral infections in the loss of beta cells, gradually, but not linear. The spontaneous remission, "honeymoon", clinically detected around 50% of children with T1D, is an opportune moment to study immunological events. Focusing physiological immunosuppression, extensively studied in experimental models, different populations of dendritic cells influence the onset of autoimmunity by the expansion of regulatory T cells stimulated via IL-10, TGFß, indoleamine 2,3-dioxygenase (IDO). In vitro, IDO induces the expression of HLA-G, nonclassical HLA class I molecule, in human dendritic cells, and both molecules cooperate to immunosuppression. However, there are few tools to identify cells that mediate the disease in humans. The objective of the study is to identify, in peripheral blood of patients with T1D, the expression of HLA-G, IDO, as well as other markers of activated T cells, B and dendritic. An individual assessment at different stages of the disease will be included when possible: at diagnosis, remission and subsequent developments. The data will be associated with the HLA class II genotype and humoral markers. (AU)