| Project/Area Number |
17590780
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
KUROSU Katsushi Chiba University, Graduate School of Medicine・Department of Respirology, Assistant Professor, 大学院医学研究院, 助手 (20291106)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKIGUCHI Yuichi Chiba University, Graduate School of Medicine・Department of Respirology, Associate Professor, 医学部附属病院, 講師 (30272321)
TATSUMI Koichiro Chiba University, Graduate School of Medicine・Department of Respirology, Associate Professor, 大学院医学研究院, 助教授 (10207061)
KURIYAMA Takayuki Chiba University, Graduate School of Medicine・Department of Respirology, Professor, 大学院医学研究院, 教授 (20009723)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Keywords | SEREX / idiopathic pulmonary fibrosis / CD4 positive lymphocyte / autoantibody / 間質性肺炎 / 急性増悪 |
|---|
| Research Abstract |
Consistent with hypothesis that pulmonary epithelium apoptosis would be the key to the acute exacerbation of idiopathic pulmonary fibrosis (IPF), we carried out serological identification of antigens by recombinant expression cloning (SEREX) analysis using type II alveolar cell carcinoma (A549) cell lines to identify antibodies related to acute exacerbation of IPF patients. By a survey of antibodies to the panel of recombinant autoantigens identified by SEREX analysis, five antibodies were identified as a novel candidate in acute exacerbation of IPE. Our study shows that antibody to annexin 1 was detected in 47% and 53% of the sera and BAL materials from patients with acute exacerbation of IPE. Some identical T cell receptor (TCR) Vbeta genes were identified in sequential materials during 1 to 3 months in all 10 acute exacerbation of IPF cases, suggesting that some infiltrating CD4-positive T cells shared limited epitopes expand by antigen-driven stimulation during disease extension. The each third complementarity determining region of identical TCR Vbeta genes identified in sequential materials from three acute exacerbation of IPF cases showed high homology with the N-terminal portion of annexin 1, included in the HLA-DR ligand epitopes predicted by TEPITOPE analysis. By Western blotting analysis and CD4-positive T cells responses of bronchoalveolar lavage (BAL) samples, the N-terminal portion of annexin 1 was cleaved and induced marked proliferative responses of CD4-positive T cells in those three patients. Our study demonstrated that annexin 1 as an autoantigen that raises both antibody production and T cell response in patients with acute exacerbation of IPF and that N terminal portion of annexin I would have some role in the pathogenesis of acute exacerbation of IPF patients.
|
