To describe a patient with neuromyelitis optica (NMO) whose aquaporin 4 (AQP4) antibody levels increased following treatment with interferon beta.
Prospective clinical and laboratory case report.
Institutional referral center for multiple sclerosis (MS).
One patient with an initial diagnosis of MS that was later revised to NMO.
A course of interferon beta-1a followed by conventional immunosuppression. Blood samples were collected from the onset of treatment, and clinical and laboratory assessment was performed.
Main Outcome Measures
Serum levels of AQP4 antibody and number and characteristics of neurological relapses.
After 3 relapses during a 10-month period despite interferon beta-1a treatment, the diagnosis of AQP4 antibody–positive NMO was made and treatment was switched to prednisolone and methotrexate. The AQP4 antibody titers rose dramatically during treatment with interferon beta, and then fell when conventional immunosuppressive therapy was substituted; the patient has remained relapse-free for the subsequent years.
Although previous articles have suggested that interferon beta may increase relapses in NMO, this is the first to illustrate an increase in AQP4 antibodies associated with such treatment.
Neuromyelitis optica (NMO) is a rare inflammatory demyelinating condition that predominantly affects the optic nerves and spinal cord. It has recently been associated with aquaporin 4 antibodies (AQP4-Abs),1 which are found in up to 85% of patients with NMO and are very rare in multiple sclerosis (MS).2,3 Neuromyelitis optica is a chronic relapsing condition that is now treated with immunosuppressive therapies in a similar manner to myasthenia gravis.
Neuromyelitis optica can present with a similar phenotype to MS, and thus patients may be initially misdiagnosed and treated with disease-modifying therapies such as interferon beta. Indeed, 1% of patients in an interferon beta trial for clinically isolated syndromes (ie, first attack of MS-like symptoms) retrospectively tested positive for serum AQP4-Abs.4
In contrast to MS, articles have suggested no effect or even an increase in the relapse rate when patients with AQP4-Ab–positive phenotypes are treated with interferon beta.5- 7 This might be explained by a shift in the immunological profile toward a T-helper type 2–dominated system that is likely to enhance autoantibody production, but there have been no data to support this. Here we show the results of quantitative analysis of AQP4-Abs in a patient with NMO who was given interferon beta and was subsequently treated successfully with conventional immunosuppressive therapy.
A 46-year-old woman presented with an inflammatory brainstem attack with transverse myelitis and subsequently had 2 further relapses during the next 3 years. She was diagnosed with MS and started receiving interferon beta 1-a. She had 1 relapse shortly after treatment initiation and a further 3 during a 10-month period, which led to a review of the medical records. The diagnosis was revised to NMO, supported by positive testing for serum AQP4-Abs. Her interferon beta-1a treatment was stopped, and she started taking prednisolone and methotrexate; she has remained relapse-free during the subsequent 3 years of follow-up. Serum samples stored from the onset of interferon beta-1a treatment were tested for AQP4-Abs titers in a single assay run. The titers rose dramatically during treatment with interferon beta and then fell when conventional immunosuppressive therapy was substituted (Figure).
Aquaporin 4 (AQP4) antibody titers. LETM indicates longitudinally extensive transverse myelitis; time 0, first manifestation.
Although clinical reports have suggested that interferon beta has no effect on or exacerbates NMO, and there is a mechanistic theory to explain this, this is the first article to show an increase in AQP4 antibodies and lack of a clinical response in association with interferon beta treatment. This was in direct contrast to the serological and clinical effect of subsequent immunosuppressive therapy. This article supports the view that NMO has a different pathogenesis to MS and that more conventional immunosuppression should be used to treat this antibody-mediated condition.
Correspondence: Jacqueline Palace, DM, Department of Clinical Neurology, John Radcliffe Hospital, University of Oxford, Level 3 West Wing, Oxford OX3 9DU, England (email@example.com).
Accepted for Publication: February 17, 2010.
Author Contributions: Dr Palace takes full responsibility for the data, analysis, and interpretation, and has full access to and the right to publish the data. Acquisition of data: Palace, Leite, Nairne, and Vincent. Analysis and interpretation of data: Palace and Leite. Drafting of the manuscript: Palace and Nairne. Critical revision of the manuscript for important intellectual content: Leite and Vincent. Administrative, technical, and material support: Leite. Study supervision: Palace and Vincent.
Financial Disclosure: Dr Palace reports serving on scientific advisory committees for Bayer Schering, Merck Serono, Teva, Biogen Idec, and Novartis UK. Dr Nairne reports receiving honoraria from GlaxoSmithKline for lectures, and has received reimbursement for clinical trials for Schwarz Pharma, Johnson and Johnson, UCB, Pfizer, and Ventura. Dr Vincent reports receiving funding for laboratory testing and consultant fees from Athena Diagnostics.
Funding/Support: This study was supported by grants 861/07, 829/05, and 909/09 from the Multiple Sclerosis Society (Dr Palace); the local UK clinical research network (Drs Palace and Leite); the Euromyasthenia network (Dr Leite); the Halley Stewart Trust (Dr Leite); the Oxford Biomedical Research Centre (Drs Palace and Leite); and the National Health Service, Athena Diagnostics, and RSR Ltd UK (University of Oxford).
Additional Information: The patient has given consent for her details, which have been made anonymous, to be used in publication.
Additional Contributions: Ana Cavey, RGN, Yvonne Hart, FRCP, and Paddy Waters, PhD.
Palace J, Leite MI, Nairne A, Vincent A. Interferon Beta Treatment in Neuromyelitis OpticaIncrease in Relapses and Aquaporin 4 Antibody Titers. Arch Neurol. 2010;67(8):1016-1017. doi:10.1001/archneurol.2010.188