Gene Profiling of Scleroderma Skin Reveals Robust Signatures of Disease... PDF Print E-mail
Thursday, 06 May 2010 23:05
Humphrey Gardner, Jeffrey R. Shearstone, Raj Bandaru, Tom Crowell, Matthew Lynes, Maria Trojanowska, Jaspreet Pannu, Edwin Smith, Stefania Jablonska, Maria Blaszczyk, Filemon K. Tan, and Maureen D. Mayes

ARTHRITIS & RHEUMATISM
Vol. 54, No. 6, June 2006, pp 1961–1973 DOI 10.1002/art.21894 © 2006, American College of Rheumatology

Objective.
To determine whether biopsy specimens obtained from systemic sclerosis (SSc) lesions show a distinctive gene profile, whether that gene profile is maintained in fibroblasts cultured from SSc skin biopsy specimens, and whether results from tissue obtained from multiple clinical centers can be combined to yield useful observations in this rare disease.

Methods. Biopsy samples and passaged fibroblasts were stored in RNAlater solution prior to processing for RNA. RNA from SSc and control skin biopsy specimens, as well as SSc and control explanted passage 4 fibroblasts, from 9 patients and 9 controls was hybridized to Affymetrix HG-U133A arrays. Data were analyzed using the BRB ArrayTools system. When appropriate, findings were followed up with immunohistochemical analysis or TaqMan studies.

Results. Biopsy samples obtained from patients with SSc had a robust and distinctive gene profile, with 1,800 qualifiers distinguishing normal skin from SSc skin at a significant level. The SSc phenotype was the major driver of sample clusters, independent of origin. Alterations in transforming growth factor and Wnt pathways, extracellular matrix proteins, and the CCN family were prominent. Explanted fibroblasts from SSc biopsy samples showed a far smaller subset of changes that were relatively variable between samples, suggesting that either nonfibroblast cell types or other aspects of the dermal milieu are required for full expression of the SSc phenotype.

Conclusion. SSc has a distinct gene profile that is not confounded by geographic location, indicating that extended multicenter studies may be worthwhile to identify distinct subsets of disease by transcript profiling. Explanted SSc fibroblasts show an incomplete reflection of the SSc phenotype.

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