Neuromyelitis optica (NMO) associated antigen, a water channel protein, known as aquaporin 4 (AQP4) is found both in the central and peripheral tissues. Detection of AQP4 antibody is clinically useful in differentiating between NMO and other optic neuritis or myelitis.
On cerebellum, AQP4 is found in the juxtaposed pial membrane, microvessels in the white matter, molecular layer and granular layer.
Often, AQP4 antibody is also associated with the staining of the cytoplasm of the granular cells: Such reactivity is also found in the CSF.
Image showing AQP4 transfected HEK cell system considered as having higher sensitivity and specificity.
Clinical: Neuromyelitis optica (NMO, also known as Devic's disease, ~65%) is an immune-mediated demyelinated disorder of the optic nerve and spinal cord. The disorder was previously thought to be a sub-type of multiple sclerosis (MS) but has a completely different pathophysiology. The two can be distinguished from one another by the presence of Aqp-4 antibodies and long segment spinal cord inflammation (referred to as longitudinally extensive transverse myelitis, LETM) which are seen in NMO. NMO is a relapsing and life-long illness and antibodies often remain positive indefinitely.
Treatment is different for each disorder therefore important to distinguish it from MS. NMO is often treated with immunosuppression (steroids, Azathioprine, Mycophenolate etc) and acute treatments often include plasma exchange. Rituximab which is a B-cell monoclonal antibody is used in refractory patients and more recently several new treatment options have been found to be useful in clinical trials These include Eculizumab (complement C5 inhibitor), Satralizumab (Interleukin-6 receptor blocker), Inebilizumab (CD19 B-cell monoclonal antibody) etc.