title: Aquaporin-4 antibody titration in NMO patients treated with rituximab: A retrospective study.
abstract: OBJECTIVE
  We undertook an observational retrospective study to investigate the usefulness of aquaporin-4 (AQP4) antibodies (Ab) titration in the management of patients with neuromyelitis optica (NMO) treated with rituximab (RTX) by studying (1) the correlation between AQP4-Ab titer and disease activity, (2) the influence of RTX on antibody levels, and (3) the association between AQP4-Ab levels and responsiveness to RTX.
  
  
  METHODS
  A cell-based assay was used for AQP4-Ab titration in 322 serum samples from 7 patients with NMO treated with RTX (median follow-up 65 months), according to a treatment-to-target approach. Serum samples were collected every month following standardized procedures.
  
  
  RESULTS
  (1) In group analysis, AQP4-Ab titers correlated with the disease activity, showing higher titers during and preceding relapses than during remission. However, in individual analysis, an increase in AQP4-Ab titers and CD19+ B cells did not always precede a relapse. (2) A reduction of AQP4-Ab titers in the short-term and long-term period was observed during RTX treatment. (3) Reduction of AQP4-Ab titers was observed in responder patients both 3 months after RTX infusion and in the long-term follow-up. In one nonresponder patient, AQP4-Ab levels never decreased during the treatment period.
  
  
  CONCLUSIONS
  Titration of AQP4-Abs could be useful in the clinical management of patients with NMO treated with RTX: titration before each reinfusion and 3 months after each reinfusion may provide information about responsiveness to RTX. Although a relationship among AQP4-Ab levels, disease activity, and response to RTX was observed, the usefulness of AQP4-Ab titration to predict relapses is limited.
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi (NICO) (P.V., F.M., L.G., A.B.) and Neurologia 2-CRESM (P.V., F.M., L.G., M.C., A.B.), AOU San Luigi Gonzaga, Orbassano, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Valentino
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi (NICO) (P.V., F.M., L.G., A.B.) and Neurologia 2-CRESM (P.V., F.M., L.G., M.C., A.B.), AOU San Luigi Gonzaga, Orbassano, Turin, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Marnetto
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi (NICO) (P.V., F.M., L.G., A.B.) and Neurologia 2-CRESM (P.V., F.M., L.G., M.C., A.B.), AOU San Luigi Gonzaga, Orbassano, Turin, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Granieri
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi (NICO) (P.V., F.M., L.G., A.B.) and Neurologia 2-CRESM (P.V., F.M., L.G., M.C., A.B.), AOU San Luigi Gonzaga, Orbassano, Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Capobianco
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi (NICO) (P.V., F.M., L.G., A.B.) and Neurologia 2-CRESM (P.V., F.M., L.G., M.C., A.B.), AOU San Luigi Gonzaga, Orbassano, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto