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DNA Research Advance Access published online on February 23, 2006

DNA Research, doi:10.1093/dnares/dsi020
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© The Author 2006. Kazusa DNA Research Institute.
Received September 1, 2005
Revised October 25, 2005

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Isolation and Expression Profiling of Genes Upregulated in the Peripheral Blood Cells of Systemic Lupus Erythematosus Patients

Taeko Ishii 1, Hiroaki Onda 2, Akie Tanigawa 3, Shiro Ohshima 4, Hiroshi Fujiwara 5, Toru Mima 6, Yoshinori Katada 7, Hitoshi Deguchi 8, Masaki Suemura 5, Tadao Miyake 9, Kunio Miyatake 10, Ichiro Kawase 11, Hanjun Zhao 3, Yoshiaki Tomiyama 12, Yukihiko Saeki 13, and Hiroshi Nojima 2 *

1 Department of Molecular Medicine, Graduate School of Medicine, Osaka University Suita, Japan; Division of Allergy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Japan
2 Innovation Plaza Osaka, Izumi, Japan; Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
3 Innovation Plaza Osaka, Izumi, Japan
4 Department of Molecular Medicine, Graduate School of Medicine, Osaka University Suita, Japan; Department of Rheumatology, Kawachinagano, Japan; Department of Clinical Research, Kawachinagano, Japan
5 Department of Internal Medicine, Nissay Hospital, Osaka, Japan
6 Department of Rheumatology, Kawachinagano, Japan
7 Department of Allergology, Kawachinagano, Japan
8 Department for Immunologic Diseases, Kinki-Central Hospital, Itami, Japan
9 Department of Rheumatology, Osaka General Medical Center Osaka, Japan
10 NHO Osaka-Minami Medical Center, Kawachinagano, Japan
11 Department of Molecular Medicine, Graduate School of Medicine, Osaka University Suita, Japan
12 Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, Suita, Japan
13 Department of Clinical Research, Kawachinagano, Japan

* To whom correspondence should be addressed.
Hiroshi Nojima, E-mail: snj-0212{at}biken.osaka-u.ac.jp


   Abstract

We have identified the genes whose expressions are augmented in the blood cells of the patients with systemic lupus erythematosus (SLE) using the ‘stepwise subtraction’ technique along with microarray analysis. The expression levels of these genes were assessed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) in 31 SLE patients and 30 healthy controls. We found that the transcription levels of following eight genes were significantly increased in SLE patients; interferon (IFN)-{alpha}-inducible protein 27 (IFI27), IFN-{alpha}-inducible protein IFI-15K (G1P2), IFN stimulated gene 20 kDa (ISG20), epithelial stromal interaction 1 (EPSTI1), defensin-{alpha} (DEFA3), amphiregulin (AREG) and two genes of unknown function (BLAST accession nos AL050290 and AY358224 = SLED1). In comparison with idiopathic thrombocytopenic purpura (ITP), an organ-specific autoimmune disease, IFI27, G1P2 and SLED1 were preferentially upregulated in SLE. In contrast, AREG and AL050290 were more highly expressed in ITP than in SLE. We correlated changes in gene expression and clinical/laboratory features of SLE and found that expression of ISG20, EPSTI1 and SLED1 are significantly correlated with lymphocyte counts. Genes linked to IFN are well known to influence SLE, but several other novel genes unrelated to IFN signaling we report here would be useful to understand the pathophysiology of SLE.

Keywords: stepwise subtraction; microarray; SLE; ITP; interferon; G0S2; amphiregulin.
Communicated by Mitsuo Oshimura
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