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Pediatric Rheumatology
Published in: Pediatric Rheumatology 1/2016

Open Access 01-12-2016 | Research article

Mitochondrial and oxidative stress genes are differentially expressed in neutrophils of sJIA patients treated with tocilizumab: a pilot microarray study

Authors: Ebun Omoyinmi, Raja Hamaoui, Annette Bryant, Mike Chao Jiang, Trin Athigapanich, Despina Eleftheriou, Mike Hubank, Paul Brogan, Patricia Woo

Published in: Pediatric Rheumatology | Issue 1/2016

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Abstract

Background

Various pathways involved in the pathogenesis of sJIA have been identified through gene expression profiling in peripheral blood mononuclear cells (PBMC), but not in neutrophils. Since neutrophils are important in tissue damage during inflammation, and are elevated as part of the acute phase response, we hypothesised that neutrophil pathways could also be important in the pathogenesis of sJIA. We therefore studied the gene profile in both PBMC and neutrophils of sJIA patients treated with tocilizumab.

Methods

We studied the transcriptomes of peripheral blood mononuclear cells (PBMC) and neutrophils from eight paired samples obtained from 4 sJIA patients taken before and after treatment, selected on the basis that they achieved ACR90 responses within 12 weeks of therapy initiation with tocilizumab. RNA was extracted and gene expression profiling was performed using Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. A longitudinal analysis using paired t-test (p < 0.05 and FC ≥ 1.5) was applied to identify differentially expressed genes (DEGs) between the two time points followed by ingenuity pathway analysis. Gene Set Enrichment Analysis (GSEA) and quantitative real-time PCR were then performed to verify the microarray results.

Results

Gene ontology analysis in neutrophils revealed that response to tocilizumab significantly altered genes regulating mitochondrial dysfunction and oxidative stress (p = 4.6E-05). This was independently verified with GSEA, by identifying a set of oxidative genes whose expression correlated with response to tocilizumab. In PBMC, treatment of sJIA with tocilizumab appeared to affect genes in Oncostatin M signalling and B cell pathways.

Conclusions

For the first time we demonstrate that neutrophils from sJIA patients responding to tocilizumab showed significantly different changes in gene expression. These data could highlight the importance of mitochondrial genes that modulate oxidative stress in the pathogenesis of sJIA.
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Metadata
Title
Mitochondrial and oxidative stress genes are differentially expressed in neutrophils of sJIA patients treated with tocilizumab: a pilot microarray study
Authors
Ebun Omoyinmi
Raja Hamaoui
Annette Bryant
Mike Chao Jiang
Trin Athigapanich
Despina Eleftheriou
Mike Hubank
Paul Brogan
Patricia Woo
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Pediatric Rheumatology / Issue 1/2016
Electronic ISSN: 1546-0096
DOI
https://doi.org/10.1186/s12969-016-0067-7

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