SHIMIZU Yuko    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Professor
Article types	Review article
Language	English
Peer review	Peer reviewed
Title	Neutralizing antibodies are associated with a reduction of interferon-β efficacy during the treatment of Japanese multiple sclerosis patients.
Journal	Formal name：The Tohoku journal of experimental medicine Abbreviation：Tohoku J Exp Med ISSN code：13493329/00408727
Domestic / Foregin	Domestic
Volume, Issue, Page	228(2),pp.85-92
Author and coauthor	Sato Douglas Kazutoshi, Nakashima Ichiro, Fukazawa Toshiyuki, Shimizu Yuko, Tomizawa Yuji, Yokoyama Kazumasa, Misu Tatsuro, Creeke Paul I, Farrell Rachel, Giovannoni Gavin, Itoyama Yasuto, Fujihara Kazuo, Aoki Masashi
Publication date	2012/10
Summary	Multiple sclerosis (MS) is a chronic immune-mediated inflammatory demyelinating disease of the central nervous system. Interferon-β (IFN-β) has been used as the first line therapy for MS treatment in Japan, but patients treated with IFN-β may develop antibodies, known as neutralizing antibodies (NAbs), which abrogate its therapeutic effects. Intramuscular IFN-β 1a and subcutaneous IFN-β 1b are currently available in Japan, but large-scale studies evaluating the prevalence and clinical implications of NAbs against these IFN-β preparations in MS patients have only been performed in Caucasian populations. NAbs positivity has been reported to be associated with HLA-DRB1 alleles, suggesting that the positivity might differ among populations with distinct genetic backgrounds. Clinical information and sera were collected from 229 consecutive MS patients treated with IFN-β in 4 centers in Japan. Sera were tested for NAbs using a luciferase reporter gene assay. In total, 5.2% of IFN-β-1a-treated patients (4/77) and 30.3% of IFN-β-1b-treated patients (46/152) were positive for Nabs. The frequency of NAbs was highest in patients treated for 13 to 24 months. Clinical relapse and contrast-enhancing lesions in the magnetic resonance imaging increased together with NAbs titers in this group. In conclusion, the prevalence of NAbs in Japanese MS patients is similar to that in Caucasian populations and is associated with an increase in disease activity. Therefore, routine NAbs testing is recommended also in Asian populations to ensure the early identification of patients who would benefit from a change in therapy.
DOI	10.1620/tjem.228.85
PMID	22976494