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Association of anti-NMDAR2 antibodies with the pathogenesis of neuropsychiatric systemic lupus erythematosus

Research Project

Project/Area Number 15591063
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionJICHI 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
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsNMDA 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 / N-methyl-D-asparateレセプター / SLE / NPSLE
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.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (3 results)

All 2005

All Journal Article (3 results)

  • [Journal Article] Antiribosomal P Protein Antibodies in Cerebrospinal Fluid Are Associated with Neuropsychiatric Systemic Lupus Erythematosus2005

    • Author(s)
      Yoshio T. et al.
    • Journal Title

      The Journal of Rheumatology 32巻1号

      Pages: 34-39

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Antiribosomal P protein antibodies in cerebrospinal fluid are associated with neuropsychiatric systemic lupus erythematosus2005

    • Author(s)
      Yoshio T, Hirata D, Onda K, Nara H, Minota S
    • Journal Title

      J Rheumatol 32(1)

      Pages: 34-39

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Antiribosomal P Protein Antibodies in Cerebrospinal Fluid Are Associated with Neuropsychiatric Systemic Lupus Erythematosus.2005

    • Author(s)
      Yoshio T. et al.
    • Journal Title

      The Journal of Rheumatology 32巻1号

      Pages: 34-39

    • Related Report
      2004 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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