BACKGROUND: Neuromyelitis optica (NMO, Devic disease) had been defined clinically until a novel autoantibody directed against the aquaporin-4 channel (NMO IgG antibody) was identified. Although previous studies have demonstrated that the NMO IgG antibody is not present in patients with multiple sclerosis (MS), these studies may have been biased by the inclusion of patients with inactive MS. We resolved to test for NMO antibody in a population of patients with active relapsing-remitting (RR) MS. METHODS: A total of 130 patients with RRMS previously enrolled in phase I (n = 26) and phase II (n = 104) trials of rituximab therapy were tested for serum NMO IgG antibody at the Mayo Clinic Neuroimmunology Laboratory by indirect immunofluorescence on a substrate of mouse central nervous system tissue. Serum samples were obtained at baseline before initiation of therapy. All patients had experienced at least one relapse in the year before study entry and had not received treatment with immunomodulatory agents for at least 2 months. RESULTS: None of the 130 patients with active RRMS tested positive for NMO IgG antibody. CONCLUSIONS: Our findings indicate that anti-aquaporin-4 immunoreactivity is unlikely to play a role in the pathogenesis of RRMS and support the results of previous studies suggesting that that the NMO IgG antibody is specific for NMO. Similar studies in a larger cohort will be necessary to fortify our conclusions.
BACKGROUND:Neuromyelitis optica (NMO, Devic disease) had been defined clinically until a novel autoantibody directed against the aquaporin-4 channel (NMO IgG antibody) was identified. Although previous studies have demonstrated that the NMO IgG antibody is not present in patients with multiple sclerosis (MS), these studies may have been biased by the inclusion of patients with inactive MS. We resolved to test for NMO antibody in a population of patients with active relapsing-remitting (RR) MS. METHODS: A total of 130 patients with RRMS previously enrolled in phase I (n = 26) and phase II (n = 104) trials of rituximab therapy were tested for serum NMO IgG antibody at the Mayo Clinic Neuroimmunology Laboratory by indirect immunofluorescence on a substrate of mouse central nervous system tissue. Serum samples were obtained at baseline before initiation of therapy. All patients had experienced at least one relapse in the year before study entry and had not received treatment with immunomodulatory agents for at least 2 months. RESULTS: None of the 130 patients with active RRMS tested positive for NMO IgG antibody. CONCLUSIONS: Our findings indicate that anti-aquaporin-4 immunoreactivity is unlikely to play a role in the pathogenesis of RRMS and support the results of previous studies suggesting that that the NMO IgG antibody is specific for NMO. Similar studies in a larger cohort will be necessary to fortify our conclusions.
Authors: Chris H Polman; Stephen C Reingold; Brenda Banwell; Michel Clanet; Jeffrey A Cohen; Massimo Filippi; Kazuo Fujihara; Eva Havrdova; Michael Hutchinson; Ludwig Kappos; Fred D Lublin; Xavier Montalban; Paul O'Connor; Magnhild Sandberg-Wollheim; Alan J Thompson; Emmanuelle Waubant; Brian Weinshenker; Jerry S Wolinsky Journal: Ann Neurol Date: 2011-02 Impact factor: 10.422