Endothelial cell activation and neovascularization are prominent in dermatomyositis

Journal of Autoimmune Diseases - Tập 3 Số 1 - 2006
Kanneboyina Nagaraju1, Lisa G. Rider2, Chenguang Fan1, Yi Wen Chen1, Megan Mitsak3, Rashmi Rawat3, Kathleen Patterson4, Cecilia Grundtman5, Frederick W. Miller2, Paul H. Plötz6, Eric P. Hoffman1, Ingrid E. Lundberg5
1Children's National Medical Center, Research Center for Genetic Medicine, 111 Michigan Ave NW, Washington, DC, 20010, USA
2Environmental Autoimmunity Group, NIEHS, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
3Johns Hopkins School of Medicine, Baltimore, MD, USA
4Children's Hospital Medical Center, Seattle, WA, USA
5Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Stockholm, Sweden
6Arthritis and Rheumatism Branch, NIAMS, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA

Tóm tắt

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.

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Journal of Autoimmune Diseases

Tập 3 Số 1

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