Reappraisal of aquaporin-4 astrocytopathy in Asian neuromyelitis optica and multiple sclerosis patients

Brain Pathol. 2011 Sep;21(5):516-32. doi: 10.1111/j.1750-3639.2011.00475.x. Epub 2011 Feb 14.

Abstract

Selective aquaporin-4 (AQP4) loss and vasculocentric complement and immunoglobulin deposition are characteristic of neuromyelitis optica (NMO). We recently reported extensive AQP4 loss in demyelinated and myelinated layers of Baló's lesions without perivascular immunoglobulin and complement deposition. We aimed to reappraise AQP4 expression patterns in NMO and multiple sclerosis (MS). We evaluated AQP4 expression relative to glial fibrillary acidic protein, extent of demyelination, lesion staging (CD68 staining for macrophages), and perivascular deposition of complement and immunoglobulin in 11 cases with NMO and NMO spectrum disorders (NMOSD), five with MS and 30 with other neurological diseases. The lesions were classified as actively demyelinating (n = 66), chronic active (n = 86), chronic inactive (n = 48) and unclassified (n = 12). Six NMO/NMOSD and two MS cases showed preferential AQP4 loss beyond the demyelinated areas, irrespective of lesion staging. Five NMO and three MS cases showed AQP4 preservation even in actively demyelinating lesions, despite grave tissue destruction. Vasculocentric deposition of complement and immunoglobulin was detected only in NMO/NMOSD patients, with less than 30% of actively demyelinating lesions showing AQP4 loss. Our present and previous findings suggest that antibody-independent AQP4 loss can occur in heterogeneous demyelinating conditions, including NMO, Baló's disease and MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged, 80 and over
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Aquaporin 4 / immunology*
  • Aquaporin 4 / metabolism*
  • Astrocytes / metabolism*
  • Astrocytes / pathology*
  • Child
  • Diffuse Cerebral Sclerosis of Schilder / immunology
  • Diffuse Cerebral Sclerosis of Schilder / metabolism
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Immunoglobulins / metabolism
  • Lymphocytes / pathology
  • Male
  • Middle Aged
  • Multiple Sclerosis / pathology*
  • Myelin Sheath / metabolism
  • Myelin Sheath / pathology
  • Neuromyelitis Optica / immunology
  • Neuromyelitis Optica / pathology*
  • Up-Regulation / genetics
  • Up-Regulation / physiology

Substances

  • AQP4 protein, human
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Aquaporin 4
  • CD68 antigen, human
  • Glial Fibrillary Acidic Protein
  • Immunoglobulins