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

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

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.

Login to download your own copy of the full and original article from the link provided below.

More articles :

» Researchers Find Small Group Of ANA & RP Negative Patients

There exists a very small subgroup of patients with (SSc) who lack circulating (ANA) and who do not have Raynaud's phenomenon (RP), research shows. These patients also fail to meet any of the diagnostic criteria for known SSc mimics.The...

» Erectile Dysfunction is Frequent in Systemic Sclerosis and Associated with Severe Disease: A Study of the EULAR Scleroderma Trial and Research Group

Chingching Foocharoen, Alan Tyndall, Eric Hachulla, Edoardo Rosato, Yannick Allanore, Dominique Farge-Bancel, Paola Caramaschi, Paolo Airó, Starovojtova M Nikolaevna, José A Pereira da Silva, Bojana Stamenkovic, Gabriela Riemekasten, Simona...

» Recent Study Shows That Stress Can Promote Disease Progression

Stress wreaks havoc on the mind and body. For example, psychological stress is associated with greater risk for depression, heart disease and infectious diseases. But, until now, it has not been clear exactly how stress influences disease and...

» Basal Activation of Type I Interferons (Alpha2 and Beta) and 2'5'OAS Genes

Danilo Bretas de Oliveira, Gabriel Magno de Freitas Almeida, Antonio Carlos Martins Guedes, Flavia Patrıcia Sena Teixeira Santos, Claudio Antonio Bonjardim, Paulo Cesar Peregrino Ferreira, and Erna Geessien KroonReceived 15 June 2011; Revised 10...

» Scleroderma Renal Crisis: A Pathology Perspective

Ibrahim Batal, Robyn T. Domsic, Thomas A.Medsger Jr., and Sheldon BastackyInternational Journal of RheumatologyVolume 2010, Article ID 543704Scleroderma renal crisis (SRC) is an infrequent but serious complication of systemic sclerosis (SSc). It is...

» Understanding The Female Bias For Autoimmune Diseases

The reasons why women are so much more commonly affected by autoimmune disease have largely remained a complex mystery. Now, however, researchers from the have identified a previously unknown type of B cell in aged female mice and in young...