Research article

Duration of chronic inflammation alters gene expression in muscle from untreated girls with juvenile dermatomyositis

Yi-Wen Chen^1,2* , Rongye Shi¹ , Nicholas Geraci³ , Sheela Shrestha³ , Heather Gordish-Dressman¹ and Lauren M Pachman^3,4*

¹  Center for Genetic Medicine Research, Children's National Medical Center, Washington DC, USA

²  Department of Pediatrics, George Washington University, Washington DC, USA

³  The Cellular and Molecular Pathobiology program of The Children's Memorial Research Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

⁴  Department of Pediatrics, The Division of Rheumatology, The Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

author email corresponding author email* Contributed equally

BMC Immunology 2008, 9:43doi:10.1186/1471-2172-9-43

Published:	31 July 2008

Abstract

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 than 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 remodelling 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, clusterin, 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.

Conclusion

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.