Expression profiling of PBMC-based diagnostic gene markers isolated from vasculitis patients.
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.
Kobayashi
Shigeto
S
Department of Rheumatology and Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Ito
Akihiko
A
Okuzaki
Daisuke
D
Onda
Hiroaki
H
Yabuta
Norikazu
N
Nagamori
Ippei
I
Suzuki
Kazuo
K
Hashimoto
Hiroshi
H
Nojima
Hiroshi
H
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D015854:Up-Regulation; D014657:Vasculitis / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; C508073:G0S2 protein, human; D005819:Genetic Markers