| Budget Amount *help |
¥3,730,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Purpose: To identify gene expression pattern of peripheral blood and salivary epithelial cells from patients with Sjogren's syndrome (SS), DNA microarray analysis was performed.
Methods: 14 primary SS (14 females, 59.3± 13.8 year-old), 5 secondary SS patients (5 females, 60.6 ±5.0 year-old) were subjected for the study. All patients fulfilled the 1999 revised Japanese criteria for SS. Total RNA was isolated with PAX gene Blood RNA system immediately after blood collection. DNA microarray analysis was done using a low density cDNA microarray system with 778 genes (Japan Genome Solutions). Reference RNA was from ten healthy donors (5 males and 5 females, mean age 39.3 year-old). Ten patients with rheumatoid arthritis (RA) were served as disease control. The relationship of gene signature with various clinical parameters, such as disease duration, symptoms and signs, complications, immunological findings, salivary and lacrimal functions was analyzed. Cultured salivary epithelial cells from
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three SS patients were subjected for DNA microarray analysis, and compared with normal salivary epithclial cells. Results: I)IFN-inducible genes were upregulated in primary and secondary SS. 2) The gene expression pattern of primary and secondary SS was similar, but was different from RA. There were several genes that could distinguish primary SS from secondary SS, some of which were IFN-inducible genes. IFN gene signature was more prominent in primary SS compared to secondary SS. 3) The expression level of interferon alpha-inducible protein 27 (IFI27) showed significantly positive correlation with serum IgG level in SS (r=0.600, p<0.01). 4) Many ribosomal protein genes were upregulated in SS patients with maltoma. When the gene-expression was compared before and after chemotherapy, the expression level of ribosomal protein S27 and S29 was decreased in an SS patient with maltoma. 5) There was not significant gene expression pattern in SS salivary epithelial cells compared with normal salivary epithelial cells. Conclusions: SS peripheral blood has unique gene signature compared to RA. IFN-inducible gene signature may be related to greater immunological abnormality. By using such molecules as ribosomal protein S27 and S29, molecular prediction of lymphoma development might be possible in SS. Less
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