Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative opticospinal multiple sclerosis in Japanese

Mult Scler. 2009 Jul;15(7):834-47. doi: 10.1177/1352458509104595. Epub 2009 May 22.

Abstract

Background: Antibodies to aquaporin-4 (AQP4) are found in a fraction of Japanese opticospinal multiple sclerosis (OSMS) patients. However, it remains unknown whether anti-AQP4 antibody-positive and negative OSMS patients possess an identical disease.

Objective: The objective of the current study was to clarify immunological differences between the two groups of patients.

Methods: We studied the serum antibody titers against AQP4 in 191 patients with idiopathic central nervous system demyelinating diseases and clarified their relationships with immunological parameters.

Results: Anti-AQP4 antibody positivity rate was higher in patients with OSMS (21/58, 36.2%), idiopathic recurrent myelitis (4/17, 23.5%), and recurrent optic neuritis (7/26, 26.9%), than in conventional MS (CMS) patients (6/90, 6.7%) and patients with other diseases (0/87). Anti-AQP4 antibody titer was significantly higher in patients with SS-A/B antibodies than in those without them. Anti-AQP4 antibody-negative OSMS patients showed significantly higher CD4(+)IFN-gamma(+)IL-4(-)T cell percentages and intracellular IFN-gamma/IL-4 ratios than anti-AQP4 antibody-positive patients, anti-AQP4 antibody-negative CMS patients, and healthy controls, and CD4(+)IFN-gamma(+)IL-4(-)T cell percentages were negatively correlated with anti-AQP4 antibody titers.

Conclusion: Anti-AQP4 antibody-positive patients are immunologically distinct from anti-AQP4 antibody-negative OSMS patients owing to a Th2 shift in the former group in comparison to a Th1 shift in the latter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aquaporin 4 / immunology*
  • Asian People*
  • Autoantibodies / blood*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • Humans
  • Immunoglobulin G / blood*
  • Interferon-gamma / blood
  • Interleukin-4 / blood
  • Japan
  • Magnetic Resonance Imaging
  • Multiple Sclerosis, Chronic Progressive / ethnology
  • Multiple Sclerosis, Chronic Progressive / immunology*
  • Multiple Sclerosis, Chronic Progressive / pathology
  • Multiple Sclerosis, Relapsing-Remitting / ethnology
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Neuromyelitis Optica / ethnology
  • Neuromyelitis Optica / immunology*
  • Neuromyelitis Optica / pathology
  • Optic Neuritis / ethnology
  • Optic Neuritis / immunology*
  • Optic Neuritis / pathology
  • Predictive Value of Tests
  • Reproducibility of Results
  • Spinal Cord / pathology
  • Syndrome

Substances

  • AQP4 protein, human
  • Aquaporin 4
  • Autoantibodies
  • IL4 protein, human
  • Immunoglobulin G
  • Interleukin-4
  • Interferon-gamma