Association of hippocampal atrophy with cerebrospinal fluid antibodies against the NR2 subtype of the N-methyl-D-aspartate receptor in patients with systemic lupus erythematosus and patients with primary Sjögren's syndrome

Arthritis Rheumatol. 2014 Dec;66(12):3387-94. doi: 10.1002/art.38852.

Abstract

Objective: Cognitive dysfunction is common in both systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS). Antibodies against the NR2 subtype of the N-methyl-D-aspartate receptor (anti-NR2 antibodies) cause hippocampal atrophy and cognitive impairment in mice and have been associated with memory impairment in both patients with SLE and patients with primary SS. In addition, a reduced volume of hippocampal gray matter has been demonstrated in both SLE and primary SS. This study was undertaken to investigate whether there is a connection between the presence of anti-NR2 antibodies and hippocampal atrophy in human diseases.

Methods: Fifty patients with SLE and 50 patients with primary SS underwent clinical examination and cerebral magnetic resonance imaging. Anti-NR2 antibodies in cerebrospinal fluid (CSF) were measured, and hippocampal gray matter volumes were compared between patients who were positive for and those who were negative for anti-NR2 antibodies.

Results: Patients with anti-NR2 antibodies in CSF had less hippocampal gray matter than patients without these antibodies. No other differences regarding gray matter volumes in other parts of the brain were identified.

Conclusion: The present findings indicate that anti-NR2 antibodies in patients with SLE and primary SS cause neuronal death manifested as reduced hippocampal gray matter, as has been previously demonstrated in mice with autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Atrophy / cerebrospinal fluid
  • Atrophy / immunology
  • Atrophy / pathology
  • Autoantibodies / cerebrospinal fluid
  • Autoantibodies / immunology*
  • Female
  • Gray Matter / pathology*
  • Hippocampus / pathology*
  • Humans
  • Image Processing, Computer-Assisted
  • Lupus Erythematosus, Systemic / cerebrospinal fluid
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Receptors, N-Methyl-D-Aspartate / immunology*
  • Sjogren's Syndrome / cerebrospinal fluid
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / pathology*

Substances

  • Autoantibodies
  • Receptors, N-Methyl-D-Aspartate