title: Transient increases in anti-aquaporin-4 antibody titers following rituximab treatment in neuromyelitis optica, in association with elevated serum BAFF levels.
abstract: Rituximab is increasingly used for prevention of relapses of neuromyelitis optica (NMO), a condition that is highly associated with serum anti-aquaporin-4 (AQP4) antibodies. However, B-cell depletion also induces systemic B-cell activating factor (BAFF), which may promote antibody production. We collected serial serum samples from a total of seven patients with NMO prior to, and following, treatment with rituximab. The samples were analyzed for anti-AQP4 antibody titer using a cell-based assay and serum BAFF levels were measured on available samples by standard enzyme-linked immunosorbent assay. Anti-AQP4 antibody levels decreased after 4 weeks to 12 weeks from the first injection of rituximab, but they increased transiently in several patients at 2 weeks after the first injection, in association with a parallel increase in serum BAFF levels. Although anti-AQP4 antibodies appear to decrease overall following rituximab treatment, our findings raise concern over the potential for an early BAFF-mediated worsening of patients with NMO receiving rituximab.
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. nakashima@em.neurol.med.tohoku.ac.jp
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakashima
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Bruce A C
authors.initials: BA
authors.lastname: Cree
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Chihiro
authors.initials: C
authors.lastname: Suzuki
authors.forename: Claude P
authors.initials: CP
authors.lastname: Genain
authors.forename: Thierry
authors.initials: T
authors.lastname: Vincent
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fujihara
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Itoyama
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000009:adverse effects*; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D053264:B-Cell Activating Factor / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009471:Neuromyelitis Optica / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D051401:Aquaporin 4; D001323:Autoantibodies; D001324:Autoantigens; D053264:B-Cell Activating Factor; C505719:TNFSF13B protein, human; D000069283:Rituximab