title: Relationship Between Neuromyelitis Optica Spectrum Disorder and Sjögren's Syndrome: Central Nervous System Extraglandular Disease or Unrelated, Co-Occurring Autoimmunity?
abstract: Sjögren's syndrome (SS) patients may be affected by the neuromyelitis optica spectrum disorder (NMOSD), a severe demyelinating syndrome associated with anti-aquaporin 4 antibodies (anti-AQP-4 antibodies). The relationship between SS and NMOSD has been a sustained focus of investigation. Among SS patients, anti-AQP-4 antibodies have been detected exclusively in those with NMOSD. It has therefore been speculated that NMOSD is not a neurologic complication of SS. However, such studies evaluated small numbers of SS patients, often mixed with other inflammatory disorders.
  
  
  
  We compared frequencies of anti-AQP-4 and SS-associated antibodies in 109 SS patients, including 11 with NMOSD, 8 with non-NMOSD demyelinating syndromes, and 90 without demyelinating syndromes.
  
  
  
  When assessed using a fluorescence-activated cell sorting (FACS) assay, anti-AQP-4 antibodies were seen exclusively in those SS patients with NMOSD (72.7%), but not in SS patients without NMOSD (P < 0.01). In contrast, anti-Ro 52, anti-Ro 60, and other autoantibodies were not more prevalent in SS patients with NMOSD versus those without. Anti-AQP-4 antibodies were detected more frequently among NMOSD patients by FACS assay than with a commercial immunohistochemical assay (72.7% versus 54.5%), despite assessment after a more prolonged period of immunosuppressive therapy (median 38 months versus 5 months; P < 0.01).
  
  
  
  The syndrome-specificity of anti-AQP-4 antibodies, along with an otherwise similar antibody profile in SS NMOSD patients, indicates that NMOSD is not a direct central nervous system manifestation of SS. Anti-AQP-4 antibodies can persist and be refractory to prolonged immunosuppressive therapy.
authors.affiliation: The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: J
authors.initials: J
authors.lastname: Birnbaum
authors.affiliation: The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: N M
authors.initials: NM
authors.lastname: Atri
authors.affiliation: The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: A N
authors.initials: AN
authors.lastname: Baer
authors.affiliation: The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: R
authors.initials: R
authors.lastname: Cimbro
authors.affiliation: The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: J
authors.initials: J
authors.lastname: Montagne
authors.affiliation: The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: L
authors.initials: L
authors.lastname: Casciola-Rosen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity / Q000502:physiology*; D002493:Central Nervous System Diseases / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D015331:Cohort Studies; D015897:Comorbidity; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D012859:Sjogren's Syndrome / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D055815:Young Adult
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies