title: Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients.
abstract: OBJECTIVE
  A novel autoimmune central nervous system (CNS) disorder with glial fibrillary acidic protein (GFAP)-IgG as biomarker was recently characterized. Here, 102 patients with GFAP-IgG positivity are described.
  
  
  METHODS
  The 102 included patients had: (1) serum, cerebrospinal fluid (CSF), or both that yielded a characteristic astrocytic pattern of mouse tissue immunostaining; (2) confirmation of IgG reactive with specific GFAP isoforms (α, ɛ, or κ) by cell-based assays; and (3) clinical data available. Control specimens (n = 865) were evaluated by tissue (n = 542) and cell-based (n = 323) assays.
  
  
  RESULTS
  Median symptom onset age was 44 years (range = 8-103), and 54% were women. The predominant phenotype (83 patients; 81%) was inflammation of meninges, brain, spinal cord, or all 3 (meningoencephalomyelitis). Among patients, highest specificity for those phenotypes was observed for CSF testing (94%), and highest sensitivity was for the GFAPα isoform (100%). Rare GFAP-IgG positivity was encountered in serum controls by tissue-based assay (0.5%) or cell-based assay (1.5%), and in CSF controls by cell-based assay (0.9%). Among patients, striking perivascular radial enhancement was found on brain magnetic resonance imaging in 53%. Although cases frequently mimicked vasculitis, angiography was uniformly negative, and spinal imaging frequently demonstrated longitudinally extensive myelitic lesions. Diverse neoplasms encountered were found prospectively in 22%. Ovarian teratoma was most common and was predicted best when both N-methyl-D-aspartate receptor-IgG and aquaporin-4-IgG coexisted (71%). Six patients with prolonged follow-up had brisk corticosteroid response, but required additional immunosuppression to overcome steroid dependency.
  
  
  CONCLUSIONS
  GFAPα-IgG, when detected in CSF, is highly specific for an immunotherapy-responsive autoimmune CNS disorder, sometimes with paraneoplastic cause. Ann Neurol 2017;81:298-309.
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN.|Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Eoin P
authors.initials: EP
authors.lastname: Flanagan
authors.affiliation: Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Hinson
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN.|Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN.|Department of Immunology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
authors.affiliation: Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Boyan
authors.initials: B
authors.lastname: Fang
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Aksamit
authors.affiliation: Department of Radiology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: P Pearse
authors.initials: PP
authors.lastname: Morris
authors.affiliation: Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Eati
authors.initials: E
authors.lastname: Basal
authors.affiliation: Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Josephe A
authors.initials: JA
authors.lastname: Honorat
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Nora B
authors.initials: NB
authors.lastname: Alfugham
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Linnoila
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN.|Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Weinshenker
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN.|Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock
authors.affiliation: Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN.|Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Andrew
authors.initials: A
authors.lastname: McKeon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D001323:Autoantibodies / Q000134:cerebrospinal fluid*; D020274:Autoimmune Diseases of the Nervous System / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002648:Child; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008875:Middle Aged; D020361:Paraneoplastic Syndromes, Nervous System / Q000134:cerebrospinal fluid*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G