AQP4IgG

AQP4-IgG are autoantibodies directed against aquaporin-4 (AQP4), a water channel expressed on astrocyte endfeet in the central nervous system. The presence of AQP4-IgG is most commonly associated with neuromyelitis optica spectrum disorder (NMOSD), a relapsing inflammatory disease characterized by optic neuritis and myelitis.

Pathophysiology: AQP4-IgG binding to AQP4 activates complement and recruits immune cells, causing astrocyte injury and blood-brain barrier disruption. The resulting astrocytopathy is followed by secondary demyelination and neuronal damage, with lesion distribution paralleling areas of high AQP4 expression such as optic nerves, spinal cord, and area postrema.

Clinical features: The disease typically presents with optic neuritis and/or longitudinally extensive transverse myelitis; area postrema syndrome (intractable nausea, vomiting, hiccups) and brainstem or diencephalic symptoms may occur.

Diagnosis: AQP4-IgG is detected in serum by cell-based assays, which have high sensitivity and specificity for NMOSD. A negative test does not completely exclude NMOSD, as some seronegative patients exist or may convert later. Distinction from multiple sclerosis is important, as treatment approaches differ.

Treatment and prognosis: Acute attacks are treated with high-dose corticosteroids and plasma exchange if refractory. Long-term management uses immunosuppressants targeting B cells or complement, such as rituximab, satralizumab, or eculizumab, to reduce relapse risk. Early diagnosis and relapse prevention improve long-term outcomes; the disease can be disabling if attacks are recurrent.