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

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.