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Aquaporin-4 antibody isoform binding specificities do not explain clinical variations in NMO

OBJECTIVE: To assess the clinical relevance of the differential binding of antibodies against the 2 main aquaporin-4 (AQP4) isoforms in neuromyelitis optica (NMO) patient sera using stably transfected human embryonic kidney cells. METHODS: Flow cytometry of human embryonic kidney cells stably transf...

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Autores principales: Kitley, Joanna, Woodhall, Mark, Leite, M. Isabel, Palace, Jackie, Vincent, Angela, Waters, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476052/
https://www.ncbi.nlm.nih.gov/pubmed/26140280
http://dx.doi.org/10.1212/NXI.0000000000000121
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author Kitley, Joanna
Woodhall, Mark
Leite, M. Isabel
Palace, Jackie
Vincent, Angela
Waters, Patrick
author_facet Kitley, Joanna
Woodhall, Mark
Leite, M. Isabel
Palace, Jackie
Vincent, Angela
Waters, Patrick
author_sort Kitley, Joanna
collection PubMed
description OBJECTIVE: To assess the clinical relevance of the differential binding of antibodies against the 2 main aquaporin-4 (AQP4) isoforms in neuromyelitis optica (NMO) patient sera using stably transfected human embryonic kidney cells. METHODS: Flow cytometry of human embryonic kidney cells stably transfected with either M23 or M1 AQP4 was used to measure antibody endpoint titers in 52 remission samples and 26 relapse samples from 34 patients with clinically well-characterized AQP4 antibody–positive NMO/NMO spectrum disorder. RESULTS: The AQP4 M23 (40–61,440) and AQP4 M1 (<20–20,480) titers varied widely between patients, as did the M23:M1 antibody ratio (1–192). In 76 of 78 samples, binding to M23 was higher than binding to M1, including during relapses and remissions (p < 0.0001), and the M23:M1 ratio was relatively constant within an individual patient. Titers usually fell after immunosuppression, but the titers at which relapses occurred varied markedly; no threshold level for relapses could be identified, and relapses could occur without a rise in titers. Relapse severity did not correlate with M23 or M1 antibody titers, although there was a correlation between the earliest M23 titers and annualized relapse rates. The M23:M1 ratio and absolute M23 and M1 titers did not relate to age at disease onset, ethnicity, disease severity, phenotype, or relapses at different anatomical sites. CONCLUSION: Relative AQP4 antibody binding to M23 and M1 isoforms differs between patients but there is no consistent association between these differences and clinical characteristics of disease. Nevertheless, the M23 isoform provided a slightly more sensitive substrate for AQP4-antibody assays, particularly for follow-up studies.
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spelling pubmed-44760522015-07-02 Aquaporin-4 antibody isoform binding specificities do not explain clinical variations in NMO Kitley, Joanna Woodhall, Mark Leite, M. Isabel Palace, Jackie Vincent, Angela Waters, Patrick Neurol Neuroimmunol Neuroinflamm Article OBJECTIVE: To assess the clinical relevance of the differential binding of antibodies against the 2 main aquaporin-4 (AQP4) isoforms in neuromyelitis optica (NMO) patient sera using stably transfected human embryonic kidney cells. METHODS: Flow cytometry of human embryonic kidney cells stably transfected with either M23 or M1 AQP4 was used to measure antibody endpoint titers in 52 remission samples and 26 relapse samples from 34 patients with clinically well-characterized AQP4 antibody–positive NMO/NMO spectrum disorder. RESULTS: The AQP4 M23 (40–61,440) and AQP4 M1 (<20–20,480) titers varied widely between patients, as did the M23:M1 antibody ratio (1–192). In 76 of 78 samples, binding to M23 was higher than binding to M1, including during relapses and remissions (p < 0.0001), and the M23:M1 ratio was relatively constant within an individual patient. Titers usually fell after immunosuppression, but the titers at which relapses occurred varied markedly; no threshold level for relapses could be identified, and relapses could occur without a rise in titers. Relapse severity did not correlate with M23 or M1 antibody titers, although there was a correlation between the earliest M23 titers and annualized relapse rates. The M23:M1 ratio and absolute M23 and M1 titers did not relate to age at disease onset, ethnicity, disease severity, phenotype, or relapses at different anatomical sites. CONCLUSION: Relative AQP4 antibody binding to M23 and M1 isoforms differs between patients but there is no consistent association between these differences and clinical characteristics of disease. Nevertheless, the M23 isoform provided a slightly more sensitive substrate for AQP4-antibody assays, particularly for follow-up studies. Lippincott Williams & Wilkins 2015-06-18 /pmc/articles/PMC4476052/ /pubmed/26140280 http://dx.doi.org/10.1212/NXI.0000000000000121 Text en © 2015 American Academy of Neurology This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
spellingShingle Article
Kitley, Joanna
Woodhall, Mark
Leite, M. Isabel
Palace, Jackie
Vincent, Angela
Waters, Patrick
Aquaporin-4 antibody isoform binding specificities do not explain clinical variations in NMO
title Aquaporin-4 antibody isoform binding specificities do not explain clinical variations in NMO
title_full Aquaporin-4 antibody isoform binding specificities do not explain clinical variations in NMO
title_fullStr Aquaporin-4 antibody isoform binding specificities do not explain clinical variations in NMO
title_full_unstemmed Aquaporin-4 antibody isoform binding specificities do not explain clinical variations in NMO
title_short Aquaporin-4 antibody isoform binding specificities do not explain clinical variations in NMO
title_sort aquaporin-4 antibody isoform binding specificities do not explain clinical variations in nmo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476052/
https://www.ncbi.nlm.nih.gov/pubmed/26140280
http://dx.doi.org/10.1212/NXI.0000000000000121
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