Aquaporin-4 IgG autoimmune syndrome and immunoreactivity associated with thyroid cancer

Tumor cells can express so-called onconeural antigens, which are normally restricted to mature neurons and glial cells in the CNS.1 The detection of neural-reactive immunoglobulin G (IgG) aids the diagnosis of paraneoplastic neurologic syndromes (PNS)1; however, the diagnostic utility and potential pathogenicity of autoantibodies vary between neurologic diseases. By contrast, anti-aquaporin-4 (AQP4) IgG from patients with neuromyelitis optica spectrum disorder (NMOSD) is a specific biomarker for NMOSD. AQP4 is the most abundant water channel in the CNS, particularly abundant on astrocytes, forming the glia limitans of the blood–brain barrier. There is compelling evidence that AQP4-IgG reactivity and pathogenicity is restricted to the CNS, probably through an impaired blood–brain barrier. The clinical features of NMOSD include inflammation of the optic nerve, spinal cord, and specific brain areas coinciding with sites of high AQP4 expression. Some cases of NMOSD thus far reported may reflect a paraneoplastic immune response.