Aquaporin-4 antibodies in patients treated with natalizumab for suspected MS

Abstract

Objective: To evaluate (1) the frequency of aquaporin-4 antibody (AQP4-ab)-seropositive cases among patients treated with natalizumab (NAT) and previously diagnosed with MS (MSNAT) in a nationwide cohort, (2) the clinical course of NAT-treated AQP4-ab-seropositive neuromyelitis optica spectrum disorder (NMOSD) patients (NMONAT), (3) AQP4-ab titers in NMONAT and AQP4-ab-seropositive NMOSD treated with other immunotherapies (NMOIT), and (4) immune mechanisms influencing disease activity in NMONAT. Methods: MSNAT serum samples were retrospectively screened with a cell-based assay for AQP4-IgG and titers determined by ELISA. The annualized relapse rate (ARR) and disability progression were assessed. Serum levels of proinflammatory cytokines (interleukin [IL]-1b, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, and interferon [IFN]-g) and the chemokine CXCL-10 of NMONAT patients identified in this (n 5 4) and a previous study (n 5 5) were measured by cytometric bead array and ELISA. Results: Of the 1,183 MSNAT patients (851 female, median 9 NAT infusions), only 4 (0.33%; 3 female, 1 male) had AQP4-IgG. Of these, 2 fulfilled the 2006 NMO criteria and all met the 2015 NMOSD criteria. The ARR was higher in NMONAT vs MSNAT (p 5 0.0182). All 4 NMONAT patients had relapses and 2 had an increase of disability. AQP4-ab titers were higher in NMONAT (n 5 9) vs NMOIT (n 5 13; p 5 0.0059). IL-8, IL-1b, and IFN-g serum levels were significantly higher, and CXCL-10 was significantly lower in NMONAT vs NMOIT. Conclusions: Misdiagnosis of NMOSD with MS is rare. NAT was not able to control disease activity in NMONAT patients, who had higher serum levels of AQP4-IgG and proinflammatory cytokines than patients with NMOSD treated with other immunotherapies.