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Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system characterized by severe demyelinating inflammatory attacks typically affecting the spinal cord and optic nerves. Anti-aquaporin-4(AQP4) serum autoantibodies are present in approximately 70% of NMO patients. Those antibodies probably are pathogenic and the titers are elevated during relapse as compared with those in remission. Rituximab is a chimeric monoclonal antibody directed against the CD20, a B cell surface antigen, and appears to limit relapses in NMO. Recently, rituximab is becoming one of the most promising drugs for the prevention of NMO attacks. Following rituximab treatment, decrease of anti-AQP4 antibody titer was reported previously and the titer remained low during B cell depletion. Though B cell depletion following rituximab infusion is rapid, NMO relapses within a month after treatment were reported. It is not known whether the early relapses are associated with the initiation of rituximab or not. Serial serum samples were collected from a total of 23 NMO patients prior to and following treatment with rituximab, at three institutions (2 from Montreal Neurological Institute, Montreal, Canada, 9 from the Multiple Sclerosis Center at UCSF, San Francisco, USA, and 12 from the Multiple Sclerosis Clinic, National Cancer Center, Ilsan, Korea). Levels of serum anti-AQP4 antibody and B cell activating factor belonging to tumor necrosis factor family (BAFF) were retrospectively measured in the serum samples. Anti-AQP4 antibody titer was measured using a sensitive cell-based assay, and the serum BAFF levels were subsequently measured by a standard ELISA kit. Although none of the patients developed initial worsening, anti-AQP4 antibody levels increased four-fold on average at two weeks after the first injection of rituximab, associated with a parallel increase in serum BAFF levels. Anti-AQP4 antibodies are being implicated pathophysiologically in NMO, our findings raise concern over potential for initial worsening of patients receiving rituximab, and it might be necessary to add an agent that may prevent an initial BAFF-mediated increase of anti-AQP4 antibody as a safety measure.

Read More: Anti-aquaporin 4 autoantibodies increase transiently after rituximab treatment in neuromyelitis optica: an association with B-cell activating factor