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Early Suppression of Immune Response Pathways Characterizes Children with Prediabetes in Genome-Wide Gene Expression Profiling

Laura L. Elo, Juha Mykkänen, Tuomas Nikula, Henna Järvenpää, Satu Simell, Tero Aittokallio, Heikki Hyöty, Jorma Ilonen, Riitta Veijola, Tuula Simell, Mikael Knip, Olli Simell, Riitta Lahesmaaa, Early Suppression of Immune Response Pathways Characterizes Children with Prediabetes in Genome-Wide Gene Expression Profiling. Journal of Autoimmunity 35(1), 70–76, 2010.

http://dx.doi.org/10.1016/j.jaut.2010.03.001

Abstract:

Type 1 diabetes (T1D) is caused by autoimmune destruction of insulin-producing pancreatic β 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.

BibTeX entry:

@ARTICLE{jElMyNiJxSiAiHyIlVeSiKnSiLa10a,
  title = {Early Suppression of Immune Response Pathways Characterizes Children with Prediabetes in Genome-Wide Gene Expression Profiling},
  author = {Elo, Laura L. and Mykkänen, Juha and Nikula, Tuomas and Järvenpää, Henna and Simell, Satu and Aittokallio, Tero and Hyöty, Heikki and Ilonen, Jorma and Veijola, Riitta and Simell, Tuula and Knip, Mikael and Simell, Olli and Lahesmaaa, Riitta},
  journal = {Journal of Autoimmunity},
  volume = {35},
  number = {1},
  pages = {70–76},
  year = {2010},
  keywords = {Type 1 diabetes; Prediabetes; Autoantibodies; Longitudinal data; Differential gene expression; Molecular networks; Pathway analysis},
}

Belongs to TUCS Research Unit(s): Biomathematics Research Unit (BIOMATH)

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