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.

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

 
More articles :

» Clinical Correlates Of Sleep Problems In Systemic Sclerosis: The Prominent Role Of Pain

Objective. Problems with sleep are common in patients with SSc and impact daily function. Little research, however, has examined factors associated with sleep disruption in SSc. Therefore, the objective of this study was to investigate...

» Grant To Fund Study Of Possible Links Between Water Pollution, Disease

Arkansas Children’s Hospital Research Institute scientists have been awarded a $997,000 grant to study the relationship between a common pollutant in water systems and the increase in autoimmune disease. The award was announced yesterday by the...

» Understanding Autoimmunity

What is Autoimmunity?One of the functions of the immune system is to protect the body by responding to invading microorganisms, such as viruses or bacteria, by producing antibodies or sensitized (types of white blood cells). Under normal...

» What Causes Scleroderma?

Collagen is a group of naturally occurring proteins, found exclusively in animals and especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, constituting...

» Pain Common in Systemic Sclerosis

Pain is common and can be severe in patients with systemic sclerosis, a cross-sectional analysis found.Among patients enrolled in the multicenter Canadian Scleroderma Research Group Registry, 83% experienced pain, more than one-third of them...

» Primary Biliary Cirrhosis Associated with Systemic Sclerosis: Diagnostic and Clinical Challenges

Cristina Rigamonti, Dimitrios P. Bogdanos, Maria G.Mytilinaiou, Daniel S. Smyk, Eirini I. Rigopoulou, and Andrew K. BurroughsReceived 3 June 2011; Accepted 7 September 2011Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease...