2004 Fiscal Year Final Research Report Summary
Association of anti-NMDAR2 antibodies with the pathogenesis of neuropsychiatric systemic lupus erythematosus
| Project/Area Number |
15591063
|
|---|
| 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 | JICHI MEDICAL SCHOOL |
|---|
Principal Investigator |
YOSHIO Taku Jichi Medical School, Department of Medicine, Associate Professor, 医学部, 助教授 (20221666)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | NMDA receptor snbunits NR2a and NR2b / anti-NMDA R2 antibodies / anti-dsDNA antibodies / systemic lupus erythematosus(SLE) / neuropsychiatric SLE(NPSLE) / antiribosomal P protein antibodies / endothelial cell activation |
|---|
| Research Abstract |
Firstly it was investigated whether IgG anti-NMDAR2 antibodies (anti-NR2) in the cerebrospinal fluid (CSF) and serum of patients with SLE are related to neuropsychiatric SLE (NPSLE). CSF and serum samples from 80 patients with SLE were used. They were divided into 4 groups (1^<st> group : neurologic syndromes of the central nervous system(CNS), 2^<nd> group : diffuse psychiatric/neuropsychological syndromes, 3^<rd> group : complex presentations (neurologic syndromes of the CNS+diffuse psychiatric/neuropsychological syndromes) and 4^<th> group : non-NPSLE). CSF and serum IgG anti-NR2 titers were measured by ELISA using synthetic DWEYSVWLSN peptide as the antigen. Serum IgG anti-NR2 were not significantly associated with the presence of NPSLE. CSF IgG anti-NR2 were significantly associated with the presence of NPSLE, especially complex presentations. CSF IgG anti-NR2 titers were significantly positive-correlated with each of serum CSF IgG anti-NR2 titers and CSF IgG anti-P titers in patients with NPSLE. These results suggest that the presence of IgG anti-NR2 in the CSF of patients with SLE may be associated with the appearance and development of NPSLE, especially complex presentations.
Secondly purified IgG anti-NR2 of 14 patients with SLE were tested for their ability to 1)bind to ds DNA, 2)bind to EC, 3)modulate adhesion molecule expression on EC surface and cytokine production from EC. Purified IgG of 5 normal controls were used as negative controls. Purified anti-NR2 bound to dsDNA with IgG-dose-dependence. They bound to EC and stimulated the up-regulation of adhesion molecule expression and IL-6 and IL-8 production more significantly than IgG of normal controls. These results suggest the possibility that anti-NR2 as anti-dsDNA antibodies may bind to EC surface and activate EC in SLE. Such events on EC in the central nervous system may lead to the damage of blood-brain barrier, resulting in the appearance and development of NPSLE.
|
Research Products
(2 results)
