title: Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo.
abstract: OBJECTIVE
  Severe inflammation and astrocyte loss with profound demyelination in spinal cord and optic nerves are typical pathological features of neuromyelitis optica (NMO). A diagnostic hallmark of this disease is the presence of serum autoantibodies against the water channel aquaporin-4 (AQP-4) on astrocytes.
  
  
  METHODS
  We induced acute T-cell-mediated experimental autoimmune encephalomyelitis in Lewis rats and confronted the animals with an additional application of immunoglobulins from AQP-4 antibody-positive and -negative NMO patients, multiple sclerosis patients, and control subjects.
  
  
  RESULTS
  The immunoglobulins from AQP-4 antibody-positive NMO patients are pathogenic. When they reach serum titers in experimental animals comparable with those seen in NMO patients, they augment clinical disease and induce lesions in the central nervous system that are similar in structure and distribution to those seen in NMO patients, consisting of AQP-4 and astrocyte loss, granulocytic infiltrates, T cells and activated macrophages/microglia cells, and an extensive immunoglobulin and complement deposition on astrocyte processes of the perivascular and superficial glia limitans. AQP-4 antibody containing NMO immunoglobulin injected into naïve rats, young rats with leaky blood-brain barrier, or after transfer of a nonencephalitogenic T-cell line did not induce disease or neuropathological alterations in the central nervous system. Absorption of NMO immunoglobulins with AQP-4-transfected cells, but not with mock-transfected control cells, reduced the AQP-4 antibody titers and was associated with a reduction of astrocyte pathology after transfer.
  
  
  CONCLUSIONS
  Human anti-AQP-4 antibodies are not only important in the diagnosis of NMO but also augment disease and induce NMO-like lesions in animals with T-cell-mediated brain inflammation.
authors: Department of Neuroimmunology, Medical University Vienna, Center for Brain Research, Vienna, Austria.
authors: Monika
authors: M
authors: Bradl
authors: Tatsuro
authors: T
authors: Misu
authors: Toshiyuki
authors: T
authors: Takahashi
authors: Mitsutoshi
authors: M
authors: Watanabe
authors: Simone
authors: S
authors: Mader
authors: Markus
authors: M
authors: Reindl
authors: Milena
authors: M
authors: Adzemovic
authors: Jan
authors: J
authors: Bauer
authors: Thomas
authors: T
authors: Berger
authors: Kazuo
authors: K
authors: Fujihara
authors: Yasuto
authors: Y
authors: Itoyama
authors: Hans
authors: H
authors: Lassmann
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D051401:Aquaporin 4 / Q000008:administration & dosage / Q000134:cerebrospinal fluid; D001323:Autoantibodies / Q000008:administration & dosage / Q000009:adverse effects* / Q000134:cerebrospinal fluid; D002460:Cell Line; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D055815:Young Adult
chemical_list: D051401:Aquaporin 4; D001323:Autoantibodies; D007074:Immunoglobulin G