Aquaporin-4 antibodies in patients treated with natalizumab for suspected MS
(2017) In Neurology: Neuroimmunology and NeuroInflammation 4(4).- 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... (More)
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.
(Less)
- author
- Gahlen, Anna ; Trampe, Anne Kathrin ; Haupeltshofer, Steffen LU ; Ringelstein, Marius ; Aktas, Orhan ; Berthele, Achim ; Wildemann, Brigitte ; Gold, Ralf ; Jarius, Sven and Kleiter, Ingo
- publishing date
- 2017
- type
- Contribution to journal
- publication status
- published
- in
- Neurology: Neuroimmunology and NeuroInflammation
- volume
- 4
- issue
- 4
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- scopus:85025135774
- ISSN
- 2332-7812
- DOI
- 10.1212/NXI.0000000000000363
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
- id
- 55727724-4cae-494e-8e14-fa65492f3f06
- date added to LUP
- 2026-02-05 09:21:56
- date last changed
- 2026-02-05 10:37:08
@article{55727724-4cae-494e-8e14-fa65492f3f06,
abstract = {{<p>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.</p>}},
author = {{Gahlen, Anna and Trampe, Anne Kathrin and Haupeltshofer, Steffen and Ringelstein, Marius and Aktas, Orhan and Berthele, Achim and Wildemann, Brigitte and Gold, Ralf and Jarius, Sven and Kleiter, Ingo}},
issn = {{2332-7812}},
language = {{eng}},
number = {{4}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Neurology: Neuroimmunology and NeuroInflammation}},
title = {{Aquaporin-4 antibodies in patients treated with natalizumab for suspected MS}},
url = {{http://dx.doi.org/10.1212/NXI.0000000000000363}},
doi = {{10.1212/NXI.0000000000000363}},
volume = {{4}},
year = {{2017}},
}