title: Aquaporin 4 IgG serostatus and outcome in recurrent longitudinally extensive transverse myelitis.
abstract: OBJECTIVE
  Studies focused on recurrent longitudinally extensive transverse myelitis (rLETM) are lacking.
  
  
  OBJECTIVE
  To determine the aquaporin 4 (AQP4) IgG detection rate using recombinant human APQ4-based assays in sequential serum specimens collected from patients with rLETM categorized as negative by first-generation tissue-based indirect immunofluorescence (IIF) assay and to define the clinical characteristics and motor disability outcomes in AQP4-IgG-positive rLETM.
  
  
  METHODS
  A search of the Mayo Clinic computerized central diagnostic index (October 1, 2005, through November 30, 2011), cross-linked with the Neuroimmunology Laboratory database, identified 48 patients with rLETM, of whom 36 (75%) were positive and 12 (25%) negative for neuromyelitis optica (NMO) IgG (per IIF of serial serum specimens). Stored serum specimens from "seronegative" patients were retested with recombinant human AQP4-based assays, including enzyme-linked immunosorbent, transfected cell-based, and fluorescence-activated cell-sorting assays. Control patients included 140 AQP4-IgG-positive patients with NMO, of whom a subgroup of 20 initially presented with 2 attacks of transverse myelitis (rLETM-onset NMO).
  
  
  METHODS
  AQP4-IgG serostatus, clinical characteristics, and Expanded Disability Status Scale score.
  
  
  RESULTS
  Six patients with negative IIF results were reclassified as AQP4-IgG positive, yielding an overall AQP4-IgG seropositivity rate of 89%. Fluorescence-activated cell-sorting, cell-based, and enzyme-linked immunosorbent assays improved the detection rate to 89%, 85%, and 81%, respectively. The female to male ratio was 2:3 for AQP4-IgG-negative rLETM and 5:1 for AQP4-IgG-positive patients. The AQP4-IgG-positive patients with rLETM or rLETM-onset NMO were similar in age at onset, sex ratio, attack severity, relapse rate, and motor disability. From Kaplan-Meier analyses, 36% of AQP4-IgG-positive patients with rLETM are anticipated to need a cane to walk within 5 years after onset. For patients with rLETM-onset NMO, the median time from onset to first optic neuritis attack (54 months) was similar to the median disease duration for AQP4-IgG-positive patients with rLETM (59 months). The median number of attacks was 3 for AQP4-IgG-positive patients with rLETM (range, 2-22), and the first optic neuritis attack for those with rLETM-onset NMO followed a median of 3 myelitis attacks (range, 2-19). Immunosuppressant therapy reduced the relapse rate in both AQP4-IgG-positive and AQP4-IgG-negative patients with rLETM.
  
  
  CONCLUSIONS
  Recombinant antigen-based assays significantly increase AQP4-IgG detection in patients with rLETM, and AQP4-IgG-negative adults with rLETM are rare. Evolution to NMO can be anticipated in AQP4-IgG-positive patients. Early initiation of immunotherapy may result in a more favorable motor outcome.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: James P
authors.initials: JP
authors.lastname: Fryer
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota2Department of Neurology, Mayo Clinic, Rochester, Minnesota3Department of Immunology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota2Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Andrew
authors.initials: A
authors.lastname: McKeon
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Jenkins
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Carin Y
authors.initials: CY
authors.lastname: Smith
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Amy M L
authors.initials: AM
authors.lastname: Quek
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Weinshenker
authors.affiliation: Department of Neurology, Mayo Clinic, Scottsdale, Arizona.
authors.forename: Dean M
authors.initials: DM
authors.lastname: Wingerchuk
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, Florida.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Shuster
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota2Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D051401:Aquaporin 4 / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009188:Myelitis, Transverse / Q000145:classification / Q000175:diagnosis / Q000276:immunology*; D009471:Neuromyelitis Optica / Q000145:classification / Q000175:diagnosis / Q000276:immunology*; D012008:Recurrence; D012042:Registries; D012737:Sex Factors; D055815:Young Adult
chemical_list: D051401:Aquaporin 4; D007074:Immunoglobulin G