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Modeling Transcriptional Rewiring in Neutrophils Through the Course of Treated Juvenile Idiopathic Arthritis

Zihua Hu1,2,3, Kaiyu Jiang4, Mark Barton Frank5

  • 1Center for Computational Research, New York State Center of Excellence in Bioinformatics & Life Sciences, State University of New York at Buffalo, Buffalo, NY, 14260, USA. zihuahu@ccr.buffalo.edu.

Scientific Reports
|May 19, 2018
PubMed

Insights

Juvenile idiopathic arthritis (JIA) neutrophils show altered gene expression. Therapy significantly reshapes these networks, with inactive disease resembling healthy controls more closely.

Area of Science:

  • Immunology
  • Genetics
  • Pediatrics

Background:

  • Neutrophils in polyarticular juvenile idiopathic arthritis (JIA) exhibit abnormal transcriptional patterns linked to metabolic issues.
  • Understanding therapy's impact on gene expression in JIA is crucial.

Purpose of the Study:

  • To investigate the effects of therapy on mRNA and miRNA expression networks in polyarticular JIA.
  • To compare transcriptional profiles across untreated active JIA, treated active JIA, and inactive JIA states.

Main Methods:

  • Utilized exon and miRNA microarrays to analyze gene expression in children with JIA and healthy controls.
  • Compared gene expression profiles in untreated active JIA (ADU), treated active JIA (ADT), and inactive disease (ID) groups against healthy controls (HC).

Main Results:

  • Therapy induced significant re-ordering of mRNA and miRNA expression networks.
  • Each disease state (ADU, ADT, ID) had a distinct transcriptional profile, with ADT differing most from HC.
  • Inactive disease (ID) profiles more closely resembled healthy controls (HC) than active disease states.
  • mRNA and miRNA expression changes were mirrored, indicating coordinated regulation.
  • Therapeutic response is complex, not a simple linear gene correction process.

Conclusions:

  • Therapy substantially alters gene expression networks in polyarticular JIA.
  • Combinatorial regulation by miRNA and transcription factors (TFs) may drive dynamic transcriptome changes during treatment.
  • Distinct transcriptional states exist for untreated active, treated active, and inactive JIA.

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