Relationship Between Neuromyelitis Optica Spectrum Disorder and Sjögren's Syndrome: Central Nervous System Extraglandular Disease or Unrelated, Co-Occurring Autoimmunity?

Arthritis Care Res (Hoboken). 2017 Jul;69(7):1069-1075. doi: 10.1002/acr.23107.

Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aquaporin 4 / blood*
  • Autoantibodies / blood
  • Autoimmunity / physiology*
  • Central Nervous System Diseases / blood
  • Central Nervous System Diseases / diagnosis
  • Central Nervous System Diseases / epidemiology
  • Cohort Studies
  • Comorbidity
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuromyelitis Optica / blood*
  • Neuromyelitis Optica / diagnosis
  • Neuromyelitis Optica / epidemiology*
  • Sjogren's Syndrome / blood*
  • Sjogren's Syndrome / diagnosis
  • Sjogren's Syndrome / epidemiology*
  • Young Adult

Substances

  • AQP4 protein, human
  • Aquaporin 4
  • Autoantibodies