Journal Article

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

Shigeto Kobayashi, Akihiko Ito, Daisuke Okuzaki, Hiroaki Onda, Norikazu Yabuta, Ippei Nagamori, Kazuo Suzuki, Hiroshi Hashimoto and Hiroshi Nojima

in DNA Research

Published on behalf of Kazusa DNA Research Institute

Volume 15, issue 4, pages 253-265
Published in print August 2008 | ISSN: 1340-2838
Published online June 2008 | e-ISSN: 1756-1663 | DOI: http://dx.doi.org/10.1093/dnares/dsn014

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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.

Keywords: vasculitis; angiitis; G0S2; EGR1; amphiregulin; hemoglobin delta

Journal Article.  6822 words.  Illustrated.

Subjects: Genetics and Genomics

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