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OBJECTIVE: To investigate an association between serum B cell activating factor of TNF family (BAFF) levels and anti-aquaporin-4 (AQP4) antibody titers in patients with neuromyelitis optica (NMO) after rituximab treatment. BACKGROUND: Anti-AQP4 antibodies are present in approximately 70% of NMO patients. Such antibodies are probably pathogenic and the titers are elevated during relapse as compared with those in remission. Rituximab is a chimeric monoclonal antibody directed against CD20. Rituximab appears to limit relapses in NMO and is becoming one of the most promising drugs. However, it is known that rituximab treatment induces serum BAFF, which is a cytokine-associated with antibody production in autoimmune diseases. DESIGN/METHODS: Three serial serum samples were collected from a total of seven NMO patients after rituximab treatment (week 0, week 2, and week 4-12). Anti-AQP4 antibody titers were measured simultaneously in all the samples using a cell-based assay, and serum BAFF levels in five patients were subsequently measured by a standard ELISA kit. RESULTS: At week 2, anti-AQP4 antibody titers increased compared to week 0 in three patients (43%) in association with increased serum BAFF levels. The highest serum BAFF levels were associated with greater increases of anti-AQP4 antibody titer (r=0.553), and in the three patients whose anti-AQP4 antibody titers rose at week 2, the serum BAFF levels were higher than 8,000 pg/ml. By one month after rituximab initiation, the serum BAFF levels had tended to decrease and the anti-AQP4 antibody titers were significantly decreased at week 4-12 compared to their titers at week 2. CONCLUSIONS/RELEVANCE: The increase of serum BAFF levels after rituximab treatment in NMO patients might have induced a transient increase of the serum anti-AQP4 antibody titers. Although increased titers of anti-AQP-4 antibody may not be the only factor underlying relapses, our finding raises the possibility that rituximab initiation could be coupled with an immune therapy targeting BAFF signaling. Supported by: KAKENHI (19209032, 20390241, 21790828) of The Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and by the Health and Labour Sciences Research Grant on Intractable Diseases (Neuroimmunological Diseases) from the Ministry of Health, Labour and Welfare of Japan.

Read More: Anti-Aquaporin 4 Antibodies Increase Transiently after Rituximab Treatment in Neuromyelitis Optica with an Association of B Cell Activating Factor