RESUMEN
OBJECTIVE: Characterization of partial remission using the insulin dose-adjusted HbA1c (IDAA1c) ≤ 9 definition in a multiethnic Brazilian population of children and adolescents with type 1 diabetes (T1D), in addition with the determination of both Class II HLA genotype and autoantibodies. METHODS: We analyzed the prevalence of partial remission in 51 new-onset T1D patients with a median time follow-up of 13 months from diagnosis. For this study, anti-GAD65, anti-IA2 and HLA class II genotyping were considered. RESULTS: Partial remission occurred in 41.2% of T1D patients until 3 months after diagnosis, mainly in those aged 5-15 years. We have demonstrated a significant increase in the haplotypes of class II HLA DRB1*0301-DQB1*0201 in children and adolescents with a partial remission phase of the disease (42.9% vs 21.7% in non-remitters, P = .0291). This haplotype was also associated with the reduction of anti-IA2 antibodies production. Homozygote DRB1*03-DQB1*0201/DRB1*03-DQB1*0201 children had the lowest prevalence of IA-2A antibodies (P = .0402). However, this association does not correlate with the time of the remission phase. CONCLUSION: Although the number of patients studied was reduced, our data suggested that the association between genetics and decrease in antibody production to certain islet auto-antigen may contribute, at least in part, to the remission phase of T1D.
Asunto(s)
Autoanticuerpos/biosíntesis , Diabetes Mellitus Tipo 1 , Antígenos de Histocompatibilidad Clase II/genética , Adolescente , Adulto , Autoanticuerpos/genética , Brasil/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/patología , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Antígenos HLA-DQ/genética , Cadenas HLA-DRB1/genética , Haplotipos , Humanos , Lactante , Masculino , Remisión Espontánea , Adulto JovenRESUMEN
BACKGROUND: Both Th1 and Th17 cells specific for neuroantigen are described as encephalitogenic in the experimental autoimmune encephalomyelitis (EAE) model. AIM: The proposal of this study was to investigate how carbon nanotubes internalized by antigen-presenting cells (APCs) affect the development of encephalitogenic CD4(+) T cells. METHODS: Therefore, we stimulated encephalitogenic T cells in the presence or not of multiwalled carbon nanotube (MWCNT). After the incubation, we analyzed the expression profile of the encephalitogenic T cells and their capacity to induce EAE. RESULTS: Encephalitogenic CD4(+) T cells cultured with APCs that were previously incubated with MWCNTs do not express IL-17. The adoptive transfer of these cells causes less severe EAE than the transfer of both Th1 and Th17 cells that are not incubated with MWCNTs. These results suggest that the increased IL-27 level produced by the APCs incubated with the carbon nanotubes inhibits the development of Th17 cells. This observation is confirmed by the concomitant reduction in the level of RORγt, which is a transcription factor essential for the development of Th17 cells. Moreover, the incubation of encephalitogenic T cells devoid of Th17 cells with neutralizing anti-IL-27 antibodies restored the production of IL-17. CONCLUSION: This finding confirms the suppressive effect of IL-27 on encephalitogenic Th17 cells. The results presented suggest that the stimulation of APCs with carbon nanoparticles prior to neuroantigen presentation affects the development of the Th17 subset of encephalitogenic CD4(+) T lymphocytes and results in less severe EAE.
