title: Aquaporin-4 autoantibodies in a paraneoplastic context.
abstract: BACKGROUND
  The neuromyelitis optica IgG autoantibody (NMO-IgG) is a validated biomarker for NMO and an emerging spectrum of inflammatory central nervous system-demyelinating disorders. Its antigen is the astrocytic water channel aquaporin-4; NMO-IgG has not been described in a cancer context.
  
  
  OBJECTIVE
  To report (1) neurologic and oncologic correlates for patients incidentally identified as NMO-IgG seropositive in a blinded evaluation for paraneoplastic autoantibodies and (2) the frequency of cancer in NMO-IgG-seropositive patients.
  
  
  METHODS
  Observational, retrospective case series.
  
  
  METHODS
  Neuroimmunology Laboratory and Neurology Clinical Practice, Mayo Clinic College of Medicine.
  
  
  METHODS
  From 1998 to 2007, we detected NMO-IgG in 2 patient groups: (1) 31 patients (88% female) identified incidentally among 180 000 patients evaluated for paraneoplastic autoantibodies and (2) 141 patients identified through physician-requested serological evaluation for a suspected NMO-spectrum disorder.
  
  
  RESULTS
  In the first group, clinical information was available for 28 patients (90%). An NMO-spectrum disorder was diagnosed in 26 patients (93%), of whom 6 had a neoplasm (5 carcinomas [2 breast, 1 lung, 1 thymic, and 1 uterine cervical] and 1 B-cell lymphoma) and 1 had monoclonal gammopathy. In 4 patients, NMO-related symptoms followed neoplasia detection (median, 14 [range 3-18] months), and in 2 patients, symptoms preceded neoplasia detection (by 5 and 3 months). Two patients had carcinoma (1 breast and 1 lung) without neurological evidence of an NMO-spectrum disorder. In the second group, neoplasms were recorded in 7 seropositive patients (5.0%) with a clinically diagnosed NMO-spectrum disorder: 3 carcinomas (all breast), 1 thyroid Hürthle cell, 1 carcinoid, 1 pituitary somatotropinoma, and 1 B-cell lymphoma. An eighth patient had monoclonal gammopathy.
  
  
  CONCLUSIONS
  Aquaporin-4-specific IgG in some cases of NMO may reflect a paraneoplastic immune response. The clinical utility of this autoantibody as a cancer marker warrants prospective investigation.
authors.affiliation: Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D020274:Autoimmune Diseases of the Nervous System / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis; D015897:Comorbidity; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000276:immunology*; D009471:Neuromyelitis Optica / Q000276:immunology; D020361:Paraneoplastic Syndromes, Nervous System / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology; D010265:Paraproteinemias / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology; D011237:Predictive Value of Tests; D012189:Retrospective Studies
chemical_list: D051401:Aquaporin 4; D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G