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RNA-Seq of CD19+ B-cell populations from patients with juvenile dermatomyositis and controls

ABSTRACT: RNA-Seq of CD19+ B-cell populations from patients with juvenile dermatomyositis and controls

PROVIDER: PRJEB20137 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR1898480_1.fastq.gz	Fastqsanger.gz
	ERR1898480_2.fastq.gz	Fastqsanger.gz
	ERR1898490_1.fastq.gz	Fastqsanger.gz
	ERR1898490_2.fastq.gz	Fastqsanger.gz
	ERR1898481_1.fastq.gz	Fastqsanger.gz

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RNA-Seq of CD19+ B-cell populations from patients with juvenile dermatomyositis and controls

Project description:RNA sequencing was used to compare the transcriptional state of ex-vivo B-cells from children with Juvenile dermatomyositis (JDM) pre- and on-treatment and age-matched healthy controls. RNA was extracted from blood samples that were taken from juvenile dermatomyositis patients at diagnosis (before they received treatment) and approximately a year into treatment. The treatment included oral prednisolone, methotrexate, azathioprine, cyclophosphamide and other drugs.

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Project description:Background :To evaluate the impact of the duration of chronic inflammation on gene expression in skeletal muscle biopsies (MBx) from untreated children with juvenile dermatomyositis (JDM) and identify genes and biological processes associated with the disease progression, expression profiling data from 16 girls with active symptoms of JDM greater or equal to 2 months were compared with 3 girls with active symptoms less than 2 months. Results: Seventy-nine genes were differentially expressed between the groups with long or short duration of untreated disease. Genes involved in immune responses and vasculature remodeling were expressed at a higher level in muscle biopsies from children with greater or equal to 2 months of symptoms, while genes involved in stress responses and protein turnover were expressed at a lower level. Among the 79 genes, expression of 9 genes showed a significant linear regression relationship with the duration of untreated disease. Five differentially expressed genes--HLA-DQA1, smooth muscle myosin heavy chain, clustering, plexin D1 and tenomodulin--were verified by quantitative RT-PCR. The chronic inflammation of longer disease duration was also associated with increased DC-LAMP+ and BDCA2+ mature dendritic cells, identified by immunohistochemistry. Conclusions: We conclude that chronic inflammation alters the gene expression patterns in muscle of untreated children with JDM. Symptoms lasting greater or equal to 2 months were associated with dendritic cell maturation and anti-angiogenic vascular remodelling, directly contributing to disease pathophysiology. Keywords: Disease progression; time course

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