Early suppression of immune response pathways characterizes children with prediabetes in genome-wide gene expression profiling

J Autoimmun. 2010 Aug;35(1):70-6. doi: 10.1016/j.jaut.2010.03.001. Epub 2010 Mar 30.


Type 1 diabetes (T1D) is caused by autoimmune destruction of insulin-producing pancreatic beta cells in the islets of Langerhans. Although defects in various T cell subsets have been linked to the disease pathogenesis, mechanisms initiating or enhancing the autoimmunity in prediabetes remain poorly understood. To unravel genes and molecular pathways affected by the diabetes-associated autoimmunity, we investigated transcriptomic profiles of prospective whole-blood samples from children who have developed T1D-associated autoantibodies and eventually clinical T1D. Gene-level investigation of the data showed systematic differential expression of 520 probesets. A network-based analysis revealed then a highly significant down-regulated network of genes involved in antigen presentation as well as T-cell receptor and insulin signaling. Finally, detection of dynamic changes in the affected pathways at the early or late phases of autoimmunity showed down-regulation of several novel T1D-associated pathways as well as known key components of immune response. The longitudinal genome-wide data generated in the present study allows the detection of dynamic changes relevant to the disease that may be completely missed in conventional cross-sectional studies or in genome-wide association studies. Taken together, our analysis showed systemic high-level repression of immune response pathways associated with T1D autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / genetics
  • Child
  • Child, Preschool
  • Computational Biology
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / physiopathology
  • Early Diagnosis
  • Female
  • Gene Expression Profiling
  • Genes, T-Cell Receptor / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Immune Tolerance*
  • Insulin / metabolism
  • Male
  • Prognosis
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology


  • Insulin