AQP4positivity

AQP4 positivity refers to the detection of autoantibodies against aquaporin-4 (AQP4-IgG) in a patient’s serum or cerebrospinal fluid, or, less commonly, to the presence of AQP4 protein in tissue demonstrated by immunohistochemistry. The term is most often used in the context of neuromyelitis optica spectrum disorder (NMOSD), a central nervous system inflammatory condition.

AQP4 is the predominant water channel expressed on astrocyte endfeet at the blood-brain barrier. In AQP4-positive NMOSD, autoantibodies bind to AQP4 on astrocytes, triggering complement-mediated cytotoxicity and inflammatory injury that preferentially affects the optic nerves, spinal cord, and area postrema. This astrocytopathy can lead to demyelination and neuronal injury.

Diagnostically, AQP4-IgG testing is central to NMOSD and is typically performed with cell-based assays, which show high specificity and considerable sensitivity. Positive testing in serum supports an NMOSD diagnosis, particularly when accompanied by typical clinical events such as optic neuritis or longitudinally extensive transverse myelitis. AQP4-IgG–negative cases can occur (seronegative NMOSD), and testing for MOG antibodies can help differentiate from MOG antibody-associated disease. Tissue-based confirmation may show loss of AQP4 immunoreactivity in active NMOSD lesions, reflecting astrocyte loss, with accompanying perivascular immunoglobulin deposition and inflammatory cells.

Clinical implications include guiding treatment choices, as AQP4-positive NMOSD often responds to B cell–depleting therapies and complement inhibitors. AQP4 positivity thus has diagnostic, prognostic, and therapeutic relevance, while recognizing the possibility of assay variability and seronegative cases.