2006 Fiscal Year Final Research Report Summary
THE MECHANISM OF NEPHRITOGENIC ANTI-DNA ANTIBODY PRODUCTION IN LUPUS NEPHRITIS
| Project/Area Number |
17591026
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
膠原病・アレルギー・感染症内科学
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
HIRABAYASHI Yasuhiko Tohoku University, Tohoku University Hospital, Lecturer (70312577)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ISHII Tomonori Tohoku University Hospital, 病院, Research Associate (10282138)
TAKASAWA Naruhiko Graduate School Of Medicine, 大学院・医学系研究科, Research Associate (50359519)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | Systemic Lupus Nephritis / Lupus Nephritis / Anti-DNA antibody |
|---|
| Research Abstract |
The aim of the present study is to elucidate the antigenic trigger for the production of human nephritogenic anti-DNA antibodies. We found that a human monoclonal nephritogenic O-81 anti-DNA antibody bound to an endoplasmic reticulum stress-inducible protein, Herp.
1. The anti-DNA or anti-Herp antibodies were obtained from the patients with active lupus nephritis by using a DNA-immobilized or a Herp-immobilized agarose, respectively. Lupus anti-DNA antibodies bound to Herp. Moreover, the anti-Herp antibodies showed specific binding to DNA.
2. Each 6-week-old BALB/c female mouse was immunized intraperitoneally with Herp or Hen Egg Lysozyme (HEL). immunization with Herp, but not HEL, elicited anti-dsDNA as well as anti-ssDNA antibodies in BALB/c mice and formed the deposits of IgG in the renal glomeruli.
3. The PBLs from SLE patients or healthy subjects were stained with a monoclonal anti-Herp antibody. Herp was spontaneously expressed in the PBLs of patients with active SLE, but in the PBLs of healthy subjects. The expression of Herp in the SLE PBLs was observed during the 72 hours in vitro culture without any stimulation. No expression of Herp was observed in healthy PBLs.
4. To assess the antigenicity of Herp, the PBLs were cultured with Herp for 6 days, and the number of anti-DNA antibody producing clones was measured by ELISPOT assay. The number of anti-DNA antibody producing clones in the PBLs from active SLE patients increased in vitro after stimulation with Herp, but not with HEL or dsDNA. The PBLs form inactive SLE patients or healthy subjects did not respond to the stimulation with Herp.
These results imply that an inducible intracellular self protein could be a trigger for human nephritogenic anti-DNA autoantibodies, where ER stress may be noted.
|
