Brain Advance Access originally published online on April 19, 2007
Brain 2007 130(5):1235-1243; doi:10.1093/brain/awm062
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Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre
1Department of Neurology, Tohoku University Graduate School of Medicine, 2Department of Neurology, Tohoku Welfare Pension Hospital and 3Department of Neurology, Konan Hospital, Sendai, Japan
Correspondence to: Toshiyuki Takahashi, MD, Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan E-mail: toshiyuki{at}em.neurol.med.tohoku.ac.jp
NMO-IgG is a disease-specific autoantibody for neuromyelitis optica (NMO) and its target antigen is aquaporin-4 (AQP4) water channel. Recently, we established a sensitive anti-AQP4 antibody assay using human AQP4-transfected cells, which appeared more sensitive than the original NMO-IgG assay. So far, there has been no large-scale study on anti-AQP4 antibody titre in NMO and related disorders. We tested 148 sera of patients with NMO, high-risk syndrome of NMO, multiple sclerosis (MS), clinically isolated syndrome suggestive of MS and miscellaneous diseases. We analysed the relation of anti-AQP4 antibody titres and clinical and laboratory parameters. The sensitivity of anti-AQP4 antibody assay was 91% (95% CI 79–100) for NMO and 85% (65–100) for high-risk syndrome, and the specificity was 100% (91–100) for NMO and high-risk syndrome, that is, none with the other disorders was positive. Among 21 anti-AQP4 antibody-positive cases whose NMO-IgG were tested, 15 were NMO-IgG-positive and 6 were NMO-IgG-negative. Higher anti-AQP4 antibody titres were associated with complete blindness and extensive or large cerebral lesions on MRI. The lengths of spinal cord lesions on MRI were positively correlated with the titres of anti-AQP4 antibody at the nadir of exacerbations. A few patients who had short (approx. one to two vertebral segments) spinal cord lesions on MRI were also seropositive with low anti-AQP4 antibody titres, but did have other clinical and MRI features of NMO. Anti-AQP4 antibody titres became lower after high-dose methylprednisolone, and a follow-up showed anti-AQP4 antibody titres remained low in relapse-free periods under immunosuppression. Cerebrospinal fluid (CSF)-anti-AQP4 antibody was detected when the serum-antibody titres exceeded 512x, at the ratio of 1 (CSF) to 500 (serum). Using a sensitive assay, the results of the present study suggest that NMO and high-risk syndrome may be essentially anti-AQP4 antibody-associated disorders, and that the anti-AQP4 antibody titres have significant clinical and immunological implications in NMO.
Key Words: neuromyelitis optica; NMO-IgG; anti-aquaporin-4 antibody; antibody titre; clinical features
Abbreviations: AQP4, aquaporin-4; AZT, azathioprine; CIS, clinically isolated syndrome suggestive of MS; CSF, cerebrospinal fluid; HIMP, high-dose intravenous methylpredonisolone; MS, multiple sclerosis; NMO, neuromyelitis optica; PE, plasma exchange; PSL, prednisolone; VS, vertebral segments
Received January 8, 2007. Revised March 5, 2007. Accepted March 7, 2007.
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