Testing for Neuromyelitis Optica (NMO)
This brings us to NMO-IgG. NMO-IgG is the first ever biomarker that is specific and sensitive for any form of central nervous system inflammatory demyelinating disease. It was discovered at the Mayo Clinic and the findings were published in 2004. NMO-IgG is 99% specific and 70% sensitive for neuromyelitis optica. It does not occur in patients with multiple sclerosis. It is important to note that multiple sclerosis has no specific biomarker.
If you look over on the right hand side of the slide, you can see in the top figure an image of a mouse cerebellum. To this slide, we have applied a patient's serum that contains NMO-IgG. The NMO-IgG fluoresces and, thus, gives you this pattern of staining. Here you can see that the peel linings of the brain are stained, that the white matter of the cerebellum is stained, and then you can also see staining around the little blood vessels that occur in the cerebellum. In the lower figure, you can see staining of the distal tubules in the kidney.
Approximately 1 year after the first paper describing NMO-IgG as a sensitive and specific biomarker for neuromyelitis optica, the target autoantigen of NMO-IgG was discovered and it was discovered to be a water channel, aquaporin-4. Aquaporin-4 not only is located in the distal tubules of the kidney, but is the most abundant water channel in the central nervous system and it is present on the astrocytic foot processes. These are the foot processes that extend out from the astrocyte. This finding has resulted in a seismic shift in how the field thinks about demyelinating diseases. It was surprising that the water channel was located on an astrocyte, rather than the oligodendrocyte, which is the cell that makes myelin. The discovery of NMO-IgG and its target autoantigen, the water channel-aquaporin-4, provided further evidence that NMO was a distinct entity from multiple sclerosis. Recent in vitro and in vivo studies support a pathogenic role for NMO-IgG and, furthermore, are beginning to define the cascade of events that lead to inflammation, demyelination, and ultimate tissue destruction.
The identification of NMO-IgG has also allowed us to recognize a broader spectrum of disease associated with this antibody. As I previously discussed with you, the fact that generally at onset of the disease patients brain MRIs are normal, I stated that contrary to traditional views we have recognized that as the disease progresses, patients commonly develop lesions on their brain scans. A recent study has shown that approximately 60% of NMO patients have brain MRI abnormalities.
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