| Project/Area Number |
09470128
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | Juntendo University |
|---|
Principal Investigator |
HASHIMOTO Hiroshi Juntendo Univ.School of Med, Professor, 医学部, 教授 (60053120)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Sigeko Juntendo Univ.School of Med, Assistant Professor, 医学部, 講師 (40186739)
TAKASAKI Yoshinari Juntendo Univ.School of Med, Associate Professor, 医学部, 助教授 (80154772)
YAGITA Hiroshi Juntendo Univ.School of Med, Associate Professor, 医学部, 助教授 (30182306)
TOKANO Yoshiaki Juntendo Univ.School of Med, Assistant Professor, 医学部, 講師 (40217469)
|
|---|
| Project Period (FY) |
1997 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | SLE / HLA-classll / children / antinuclear antibodies / CD80 / CD86 / Fas / B cell / T cell / HLA-class II / 妊娠 / アポトーシス |
|---|
| Research Abstract |
Little is known regarding the immunological abnormalities in pre-ictal SLE. In our study, the positive rate of antinuclear antibodies (ANA) is significantly higher in children born to patients with SLE (SLE children: 27.8%; 67 of 241) compared with controls (7.4%; 4 of 54). Recently, it is reported that the risk for siblings of SLE patients to develop disease is estimated to be 20 times higher than that of general population. Based on the speculation that SLE children may be prone to develop SLE in future, a follow-up study was started to analyze the course of the immmunoregulatory change in SLE children.
We investigated SLE children who were invited the outpatients clinic of the Juntendo hospital in the period from 1991 to 1999. 67 of 241 SLE children had detectable ANA. During the follow up, ANA changed to the positive in 9 cases aged from 4 to 8. In this reason, we analyzed CD4/CD8, CD3/CD19 (T cell/B cell) ratios and CD25, HLA-DR, CD80/CD86, Fas expression on the peripheral blood mo
… More
nonuclear cells (PBMC) in SLE children and controls aged from 1 to 10 by flow cytometry. 1) The CD4/CD8 ratios of SLE children transiently decreased in age 3-4. 2) Among SLE children, The CD4/CD8 ratios of ANA positive (14 cases) are significantly lower than that of ANA negative (58 cases). 3) There are significant differences of HLA-DR expression on CD3 positive cells between each age of SLE children. 4) Fas, CD80 and CD86 expression on CD3 positive cells of SLE children are significantly lower than that of controls. In SLE model mouse. Fas expression on CD5 positive B cells was biphsic with low (FasィイD1lowィエD1) and high(FasィイD1highィエD1). FasィイD1lowィエD1 population was relatively resistant to Fas mediated apoptosis and presumably autoantibody-secreting cells. To examined FasィイD1lowィエD1 population in 11 SLE children (ANA positive: 2, negative: 9), CD5 positive B cells on PBMC were stimulated with anti-CD40 mAb for 4 days and examined by now cytometry. Only 1 out or 11 had shown biphasic pattern, who had detectable ANA. The phenotypic change on immunoregulatory cells was occurred before and after production of ANA. During follow up, nobody was dignosed define SLE. This suggests that there are many steps of immunological changes to develop SLE. Further study remains to be necessary. Less
|
