* Maternal Type 1 Diabetes Reduces Autoantigen-Responsive CD4+ T Cells in Offspring.
- Autoimmunity against pancreatic β-cell autoantigens is a characteristic of childhood type 1 diabetes. Autoimmunity usually appears in genetically susceptible children with the development of autoantibodies against (pro)insulin in early childhood. The offspring of mothers with type 1 diabetes are protected from this process. The aim of this study was to determine whether the protection conferred by maternal type 1 diabetes is associated with improved neonatal tolerance against (pro)insulin. Consistent with improved neonatal tolerance, the offspring of mothers with type 1 diabetes had reduced cord blood CD4+ T cell responses to proinsulin and insulin, a reduction in the inflammatory profile of their proinsulin-responsive CD4+ T cells, and improved regulation of CD4+ T cell responses to proinsulin at 9 months of age, as compared with offspring with a father or sibling with type 1 diabetes. Maternal type 1 diabetes was also associated with a modest reduction in CpG methylation of the INS gene in cord blood mononuclear cells from offspring with a susceptible INS genotype. Our findings support the concept that a maternal type 1 diabetes environment improves neonatal immune tolerance against the autoantigen (pro)insulin.
* Prognostic significance of the tumor suppressor protein p53 gene in childhood acute lymphoblastic leukemia.
- The tumor suppressor protein p53 (TP53) gene is associated with various types of cancer; however, little is known about TP53 expression in patients with childhood acute lymphoblastic leukemia (ALL). The aim of the present study was to investigate the prognostic value of TP53 expression in childhood ALL. To achieve this, TP53 mRNA levels of 146 children with ALL and 23 child donors with idiopathic thrombocytopenic purpura were determined by reverse transcription-quantitative PCR. Relapse-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. The results demonstrated that TP53 mRNA level in patients with ALL was higher compared with that in the ITP donors (P=0.019). Patients with highly-expressed TP53 exhibited lower percentages of peripheral blood blast, higher platelet counts and inferior complete remission rates compared with patients with low expression of TP53. Survival analyses revealed that high TP53 expression was associated with poor OS and RFS in childhood ALL (P=0.018 and P=0.028, respectively) and was an independent prognostic factor in multivariate analysis for poor RFS (P<0.001) and OS (P<0.001). In conclusion, high TP53 expression is associated with poor outcomes and may be used as a molecular prognostic marker to be incorporated into an improved risk classification system for childhood ALL.