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Several international groups have used alternative tests employing the specific aquaporin-4 (AQP4) protein antigen of NMO used in the current trial.

Japanese scientists, many of whom have collaborated with the Mayo team in the past, tested an anti-AQP4 antibody assay using human AQP4-transfected cells, which they reported appeared to be more sensitive than the NMO-IgG assay. The findings were reported last May in the journal Brain.

Among 21 anti-AQP4 antibody-positive cases whose NMO-IgG were tested,15 were NMO-IgG-positive and six were NMO-IgG-negative. In 148 patients with NMO, high-risk syndrome of NMO, MS, clinically isolated syndrome suggestive of MS and miscellaneous diseases, the anti-AQP4 antibody assay was 91 percent (CI 79–100) for NMO and 85 percent (65–100) for high-risk syndrome, and the specificity was 100 percent (91–100) for NMO and high-risk syndrome. None of the patients with the other disorders tested positive.

Without the new blood tests, classic NMO can only be distinguished from MS by the extensive spinal cord lesions it inflicts spanning three or more segments of the bony spine, and by lack of MS-type lesions found by MRI of the brain.

“These alternative assays appear to be more sensitive but their diagnostic specificity needs validation in larger blinded studies of pediatric and adult patients,” Dr. Pittock said.


• Takahashi T, Fujihara K, Nakamura M, et al. Establishment of a new sensitive assay for anti-human aquaporin-4 antibody in neuromyelitis optica. J Exp Med 2006;210:307–313.
    • Takahashi T, Fujihara F, Nakashima I. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 2007;130:1235–1243.