Research

Endothelial cell activation and neovascularization are prominent in dermatomyositis

Kanneboyina Nagaraju¹, Lisa G Rider², Chenguang Fan¹, Yi-Wen Chen¹, Megan Mitsak³, Rashmi Rawat³, Kathleen Patterson⁵, Cecilia Grundtman⁶, Frederick W Miller², Paul H Plotz⁴, Eric Hoffman¹ and Ingrid E Lundberg⁶

¹  Children's National Medical Center, Research Center for Genetic Medicine, 111 Michigan Ave NW, Washington DC, 20010, USA

²  Environmental Autoimmunity Group, NIEHS, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA

³  Johns Hopkins School of Medicine, Baltimore, MD, USA

⁴  Arthritis and Rheumatism Branch, NIAMS, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA

⁵  Children's Hospital Medical Center, Seattle, WA, USA

⁶  Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden

Journal of Autoimmune Diseases 2006, 3:2doi:10.1186/1740-2557-3-2

Published:	20 February 2006

Abstract

Background

While vascular and immune abnormalities are common in juvenile and adult dermatomyositis (DM), the molecular changes that contribute to these abnormalities are not clear. Therefore, we investigated pathways that facilitate new blood vessel formation and dendritic cell migration in dermatomyositis.

Methods

Muscle biopsies from subjects with DM (9 children and 6 adults) and non-myositis controls (6 children and 7 adults) were investigated by immunohistochemistry using antibodies that recognize existing (anti-CD146) and newly formed blood vessels (anti-αVβ3) and mature dendritic cells (anti-DC-LAMP). Blood vessel quantification was performed by digitalized image analysis. Additional muscle biopsies from subjects with adult DM and non-myositis controls were used for global gene expression profiling experiments.

Results

A significant increase in neovascularization was found in muscle biopsies of DM patients; neovascularization (αVβ3 positive capillaries and vessels per muscle fiber) was much higher in juvenile than in adult DM patients (control vs juvenile DM: Mean ± SE: 0.06 ± 0.01 vs 0.6 ± 0.05; p < 0.0001 and control vs adult DM: Mean ± SE: 0.60 ± 0.1 vs 0.75 ± 0.1; p = 0.051). Gene expression analysis demonstrated that genes that participate not only in angiogenesis but also in leukocyte trafficking and the complement cascade were highly up regulated in DM muscle in comparison to age matched controls. DC-LAMP positive dendritic cells were highly enriched at perivascular inflammatory sites in juvenile and adult DM patients along with molecules that facilitate dendritic cell transmigration and reverse transmigration (CD142 and CD31).

Conclusion

These results suggest active neovascularization and endothelial cell activation in both juvenile and adult DM. It is likely that close association of monocytes with endothelial cells initiate rapid dendritic cell maturation and an autoimmune response in DM.