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.