Exploring the genes associated with the response to intravenous immunoglobulin in patients with Kawasaki disease using DNA microarray analysis

Exp Mol Pathol. 2015 Feb;98(1):7-12. doi: 10.1016/j.yexmp.2014.11.006. Epub 2014 Nov 14.

Abstract

In this study we aimed to screen genes associated with intravenous immunoglobulin (IVIG) responding in patients with Kawasaki disease (KD) and thus explore the underlying molecular mechanism of IVIG resistance. The differentially expressed genes (DEGs) were identified by samr package in R. Then, protein-protein interaction (PPI) networks were constructed by STRING software. We further collected the regulatory data from TRANSFAC database, followed by regulatory interaction network construction. A total 194 of DEGs, including 185 up- and 9 down-regulated DEGs, were identified between IVIG-responding and non-responding patients with KD at acute stage. In contrast, no DEGs were found at convalescent stage. PPI networks and regulatory networks were constructed based on the 185 up-regulated genes at acute stage. The degrees of TFRC (transferrin receptor protein 1) and GADD45A (growth arrest and DNA-damage-inducible alpha) were higher than other genes, and meanwhile MYC (V-Myc Myelocytomatosis Viral Oncogene Homolog) and E2F1 (E2F Transcription Factor 1) were found to be two TFs (transcription factors) with the highest degrees. In conclusions, the response to IVIG in Kawasaki disease patients may be involved in the expression of TFRC, GADD45A, MYC and E2F1.

Keywords: Intravenous immunoglobulin; Kawasaki disease; Regulation network; Responding.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Biomarkers / metabolism*
  • Case-Control Studies
  • Cell Cycle Proteins / genetics
  • Child, Preschool
  • Computational Biology
  • E2F1 Transcription Factor / genetics
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks*
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use*
  • Infant
  • Male
  • Mucocutaneous Lymph Node Syndrome / genetics*
  • Mucocutaneous Lymph Node Syndrome / therapy*
  • Nuclear Proteins / genetics
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Proto-Oncogene Proteins c-myc / genetics
  • Receptors, Transferrin / genetics

Substances

  • Antigens, CD
  • Biomarkers
  • CD71 antigen
  • Cell Cycle Proteins
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • GADD45A protein, human
  • Immunoglobulins, Intravenous
  • MYC protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • Receptors, Transferrin