Rheumatology Advance Access published online on January 17, 2006
Rheumatology, doi:10.1093/rheumatology/kei244
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Rheumatology, Department of Internal Medicine, UT Houston Medical School, Houston, TX, USA
* To whom correspondence should be addressed. Objective. To obtain a global view of the immunological alterations occurring in early systemic sclerosis (SSc) by transcriptional profiling of peripheral blood cells (PBCs). Methods. Oligonucleotide microarrays were used to compare PBC gene expression profiles in 18 SSc cases (<2 yr duration) and 18 controls matched for race, gender and ethnicity. SSc cases had no prior or current exposure to cytotoxic drugs. PAXgene tubes were used to stabilize RNA during phlebotomy. Changes in gene expression were independently validated by real-time polymerase chain reaction. Results. SSc PBCs demonstrated differential expression of 18 interferon-inducible genes. Six of these genes were identical to the interferon signature genes in lupus peripheral blood mononuclear cells. Notably, SSc PBCs also had increased expression of allograft inflammatory factor (AIF1) and several selectins and integrins involved in cellular adhesion to the endothelium. Global analysis of 284 known biological pathways revealed that 13 were differentially regulated in SSc PBCs, including two pathways (IL2RB and GATA3) that lead to TH2 polarization. Conclusions. Transcriptional profiling reliably discriminates between PBCs from SSc and normal donors despite the fact that they represent a heterogeneous cell population. Multiple biological pathways were differentially regulated in SSc PBCs, but a common thread across these pathways was alterations in protein tyrosine kinase 2
Received September 1, 2005
Accepted November 4, 2005
Original Article
Signatures of differentially regulated interferon gene expression and vasculotrophism in the peripheral blood cells of systemic sclerosis patients
F. K. Tan 1 *,
X. Zhou 1,
M. D. Mayes 1,
P. Gourh 1,
X. Guo 1,
C. Marcum 1,
L. Jin 2,
and
F. C. Arnett Jr 1
2 Center for Genome Information, University of Cincinnati, Cincinnati, OH, USA
F. K. Tan, E-mail: filemon.k.tan{at}uth.tmc.edu
Abstract 
and mitogen-activated protein kinase signalling. Although the SSc PBC gene expression profile demonstrated some parallels with the lupus interferon gene signature, there was also increased expression of transcripts encoding proteins that target PBCs to the endothelium, which might be relevant to the vasculopathy of SSc.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Comabella, J. D. Lunemann, J. Rio, A. Sanchez, C. Lopez, E. Julia, M. Fernandez, L. Nonell, M. Camina-Tato, F. Deisenhammer, et al. A type I interferon signature in monocytes is associated with poor response to interferon-{beta} in multiple sclerosis Brain, September 9, 2009; (2009) awp228v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kruhoffer, L. Dyrskjot, T. Voss, R. L.P. Lindberg, R. Wyrich, T. Thykjaer, and T. F. Orntoft Isolation of Microarray-Grade Total RNA, MicroRNA, and DNA from a Single PAXgene Blood RNA Tube J. Mol. Diagn., September 1, 2007; 9(4): 452 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Alkassab, P. Gourh, F. K. Tan, T. McNearney, M. Fischbach, C. Ahn, F. C. Arnett, and M. D. Mayes An allograft inflammatory factor 1 (AIF1) single nucleotide polymorphism (SNP) is associated with anticentromere antibody positive systemic sclerosis Rheumatology, August 1, 2007; 46(8): 1248 - 1251. [Abstract] [Full Text] [PDF]
|
|