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DNA Research Advance Access published online on June 17, 2008
DNA Research, doi:10.1093/dnares/dsn014
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© The Author 2008. Kazusa DNA Research Institute
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Expression Profiling of PBMC-based Diagnostic Gene Markers Isolated from Vasculitis Patients

Shigeto Kobayashi1, Akihiko Ito2, Daisuke Okuzaki3,4, Hiroaki Onda3,5, Norikazu Yabuta3, Ippei Nagamori3, Kazuo Suzuki6,7, Hiroshi Hashimoto1 and Hiroshi Nojima3,4,5,*

1 Department of Rheumatology and Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
2 Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
3 Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 562-0031, Japan
4 DNA-chip Development Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 562-0031, Japan
5 Innovation Plaza Osaka, Izumi, Osaka 594-1144, Japan
6 Department of Bioactive Molecules, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
7 Inflammation Program, Department of Immunology, Chiba University, Graduate School of Medicine, Inohana 1-8-1 Chuo-ku, Chiba, 260-8670, Japan

Received 8 May 2008 ; accepted 29 May 2008.

Vasculitis (angiitis) is a systemic autoimmune disease that often causes fatal symptoms. We aimed to isolate cDNA markers that would be useful for diagnosing not only vasculitis but also other autoimmune diseases. For this purpose, we used stepwise subtractive hybridization and cDNA microarray analyses to comprehensively isolate the genes whose expressions are augmented in peripheral blood mononuclear cells (PBMCs) pooled from vasculitis patients. Subsequently, we used quantitative real-time polymerase chain reaction (qRT–PCR) to examine the mRNA levels of each candidate gene in individual patients. These analyses indicated that seven genes exhibit remarkably augmented expression in many vasculitis patients. Of these genes, we analyzed G0/G1 switch gene 2 (G0S2) further because G0S2 expression is also enhanced in the PBMCs of patients with systemic lupus erythematodes (SLE). We generated G0S2 transgenic mice that ubiquitously overexpress human G0S2. Although we did not observe any obvious vasculitis-related histopathologic findings in these mice, these mice are unhealthy as they produce only few offspring and showed elevated serum levels of two autoimmunity-related antibodies, anti-nuclear antibody, and anti-double strand DNA antibody. Thus, our large-scale gene profiling study may help finding sensitive and specific DNA markers for diagnosing autoimmune diseases including vasculitis and SLE.

Key words: vasculitis; angiitis; G0S2; EGR1; amphiregulin; hemoglobin delta

* To whom correspondence should be addressed. Tel. + 81 6-6875-3980. Fax. + 81 6-6875-5192. E-mail: snj-0212{at}biken.osaka-u.ac.jp

Edited by Mitsuo Oshimura.


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