| Project/Area Number |
16390284
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
SASAKI Takeshi TOHOKU UNIVERSITY, Professor Emeritus, 名誉教授 (50110656)
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| Co-Investigator(Kenkyū-buntansha) |
HARIGAE Hideo TOHOKU UNIVERSITY, HOSPITAL, Lecture, 病院・講師 (50302146)
ISHII Tomonori TOHOKU UNIVERSITY, HOSPITAL, Research Associate, 病院・助手 (10282138)
ISHII Keiko TOHOKU UNIVERSITY, GARDUATE SCHOOL OF MEDICINE, Associate Professor, 大学院医学系研究科, 助教授 (00291253)
宗像 靖彦 東北大学, 病院・助手 (20271950)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2006: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | rheumatoid arthritis / human parvovirus B19 / KU80 / neutralizing antibody / siRNA / ヒトパルボウィルスB19 / TNFα / ウイルス中和抗体 / si RNA / 持続感染 / レセプター / マクロファージ / T細胞 / Ku80 / P抗原 / 低酸素 |
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| Research Abstract |
1.Clinical study:
We compared clinical features of patients with rheumatoid arthritis(RA) who had or had not the evidences of human parvovirus B19 (B19) infection at the onset of RA. The result revealed no differences between the clinical profile of patients with B19 and that without B19.
2.Mechanism for the B19 infection to the targeted cells.
B19 bound to Ku80 and P antigen as the cellular receptor on on the surface of targeted cells. The entry of B19 into cells occurred using claslin. It has been suggested that there may be an unknown factor that is responsible for the intracellular transportation of B19 to nucleus.
3.Neutralizing antibody activity to B19 in rheumatoid arthritis.
Neutralizing antibodies has an important role on the host defence at B19 infection. We studied neutralizing antibody activity against B19 in patients with B19 infection and rheumatoid arthritis. The neutralizing activity was ddetermined through the ability of serum antibody to inhibit B19 infection in erythroid cell line KU812Ep6 using quantitative PCR assay. The levels of neutralizing ability elevated at symptomatic resolution in most cases with acute B19 infection. Despite the elevation of IgG anti-B19 antibodies, the neutralizing ability remained markedly low in patients with prolonged B19 infection in 41 of 62 patients with rheumatoid arthritis.
4.Inhibition of B19 proliferation by siRNA against B19.
SiRNA to B19 NS1 inhibited B19 proliferation in B19-infected erythroid cell lines. The addition of NS1 siRNA to primary culture system using RA synovial cells in vitro caused marked inhibition of TNF α proliferation, indicating a possible application of NS1 siRNA to the therapy for RA.
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