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Transient increases in anti-aquaporin-4 antibody titers following rituximab treatment in neuromyelitis optica, in association with elevated serum BAFF levels

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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.

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Acknowledgements

This study was supported by KAKENHI (19209032 and 20390241) of The Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and by the Health and Labor Sciences Research Grant on Intractable Diseases (Neuroimmunological Diseases) from the Ministry of Health, Labor and Welfare of Japan. BACC received grant support from the NINDS (K-23 NS0-48869) and Genentech.

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