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Hydroxycholesterol Levels in the Serum and Cerebrospinal Fluid of Patients with Neuromyelitis Optica Revealed by LC-Ag(+)CIS/MS/MS and LC-ESI/MS/MS with Picolinic Derivatization: Increased Levels and Association with Disability during Acute Attack

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). Hydroxycholesterols (OHCs), metabolites of CNS cholesterol, are involved in diverse cellular responses to inflammation and demyelination, and may also be involved in the pathogenesis of NMO. We a...

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Autores principales: Cha, Eunju, Lee, Kang Mi, Park, Ki Duk, Park, Kyung Seok, Lee, Kwang-Woo, Kim, Sung-Min, Lee, Jaeick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5152860/
https://www.ncbi.nlm.nih.gov/pubmed/27942009
http://dx.doi.org/10.1371/journal.pone.0167819
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author Cha, Eunju
Lee, Kang Mi
Park, Ki Duk
Park, Kyung Seok
Lee, Kwang-Woo
Kim, Sung-Min
Lee, Jaeick
author_facet Cha, Eunju
Lee, Kang Mi
Park, Ki Duk
Park, Kyung Seok
Lee, Kwang-Woo
Kim, Sung-Min
Lee, Jaeick
author_sort Cha, Eunju
collection PubMed
description Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). Hydroxycholesterols (OHCs), metabolites of CNS cholesterol, are involved in diverse cellular responses to inflammation and demyelination, and may also be involved in the pathogenesis of NMO. We aimed to develop a sensitive and reliable method for the quantitative analysis of three major OHCs (24S-, 25-, and 27-OHCs), and to evaluate their concentration in the cerebrospinal fluid (CSF) and serum of patients with NMO. The levels of the three OHCs in the serum and CSF were measured using liquid chromatography-silver ion coordination ionspray tandem mass spectrometry and liquid chromatography-electrospray ionization tandem mass spectrometry with picolinyl ester derivatization, respectively. The linear range was 5–250 ng/mL for 24S- and 27-OHC, and 0.5–25 ng/mL for 25-OHC in serum, and was 0.1–5 ng/mL for 24S- and 27-OHC, and 0.03–1 ng/mL for 25-OHC in CSF. Precision and accuracy were 0.5%–14.7% and 92.5%–109.7%, respectively, in serum, and were 0.8%–7.7% and 94.5%–119.2%, respectively, in CSF. Extraction recovery was 82.7%–90.7% in serum and 68.4%–105.0% in CSF. When analyzed in 26 NMO patients and 23 control patients, the 25-OHC (0.54 ± 0.96 ng/mL vs. 0.09 ± 0.04 ng/mL, p = 0.032) and 27-OHC (2.68 ± 3.18 ng/mL vs. 0.68 ± 0.25 ng/mL, p = 0.005) were increased in the CSF from NMO patients. When we measured the OHC(CSF) index that controls the effects of blood–brain barrier disruption on the level of OHC in the CSF, the 27-OHC(CSF) index was associated with disability (0.723; 95% confidence interval (CI)– 0.181, 0.620; p = 0.002), while the 24-OHC(CSF) index (0.518; 95% CI– 1.070, 38.121; p = 0.040) and 25-OHC(CSF) index (0.677; 95% CI– 4.313, 18.532; p = 0.004) were associated with the number of white blood cells in the CSF of NMO patients. Our results imply that OHCs in the CNS could play a role in the pathogenesis of NMO.
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spelling pubmed-51528602016-12-28 Hydroxycholesterol Levels in the Serum and Cerebrospinal Fluid of Patients with Neuromyelitis Optica Revealed by LC-Ag(+)CIS/MS/MS and LC-ESI/MS/MS with Picolinic Derivatization: Increased Levels and Association with Disability during Acute Attack Cha, Eunju Lee, Kang Mi Park, Ki Duk Park, Kyung Seok Lee, Kwang-Woo Kim, Sung-Min Lee, Jaeick PLoS One Research Article Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). Hydroxycholesterols (OHCs), metabolites of CNS cholesterol, are involved in diverse cellular responses to inflammation and demyelination, and may also be involved in the pathogenesis of NMO. We aimed to develop a sensitive and reliable method for the quantitative analysis of three major OHCs (24S-, 25-, and 27-OHCs), and to evaluate their concentration in the cerebrospinal fluid (CSF) and serum of patients with NMO. The levels of the three OHCs in the serum and CSF were measured using liquid chromatography-silver ion coordination ionspray tandem mass spectrometry and liquid chromatography-electrospray ionization tandem mass spectrometry with picolinyl ester derivatization, respectively. The linear range was 5–250 ng/mL for 24S- and 27-OHC, and 0.5–25 ng/mL for 25-OHC in serum, and was 0.1–5 ng/mL for 24S- and 27-OHC, and 0.03–1 ng/mL for 25-OHC in CSF. Precision and accuracy were 0.5%–14.7% and 92.5%–109.7%, respectively, in serum, and were 0.8%–7.7% and 94.5%–119.2%, respectively, in CSF. Extraction recovery was 82.7%–90.7% in serum and 68.4%–105.0% in CSF. When analyzed in 26 NMO patients and 23 control patients, the 25-OHC (0.54 ± 0.96 ng/mL vs. 0.09 ± 0.04 ng/mL, p = 0.032) and 27-OHC (2.68 ± 3.18 ng/mL vs. 0.68 ± 0.25 ng/mL, p = 0.005) were increased in the CSF from NMO patients. When we measured the OHC(CSF) index that controls the effects of blood–brain barrier disruption on the level of OHC in the CSF, the 27-OHC(CSF) index was associated with disability (0.723; 95% confidence interval (CI)– 0.181, 0.620; p = 0.002), while the 24-OHC(CSF) index (0.518; 95% CI– 1.070, 38.121; p = 0.040) and 25-OHC(CSF) index (0.677; 95% CI– 4.313, 18.532; p = 0.004) were associated with the number of white blood cells in the CSF of NMO patients. Our results imply that OHCs in the CNS could play a role in the pathogenesis of NMO. Public Library of Science 2016-12-12 /pmc/articles/PMC5152860/ /pubmed/27942009 http://dx.doi.org/10.1371/journal.pone.0167819 Text en © 2016 Cha et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Cha, Eunju
Lee, Kang Mi
Park, Ki Duk
Park, Kyung Seok
Lee, Kwang-Woo
Kim, Sung-Min
Lee, Jaeick
Hydroxycholesterol Levels in the Serum and Cerebrospinal Fluid of Patients with Neuromyelitis Optica Revealed by LC-Ag(+)CIS/MS/MS and LC-ESI/MS/MS with Picolinic Derivatization: Increased Levels and Association with Disability during Acute Attack
title Hydroxycholesterol Levels in the Serum and Cerebrospinal Fluid of Patients with Neuromyelitis Optica Revealed by LC-Ag(+)CIS/MS/MS and LC-ESI/MS/MS with Picolinic Derivatization: Increased Levels and Association with Disability during Acute Attack
title_full Hydroxycholesterol Levels in the Serum and Cerebrospinal Fluid of Patients with Neuromyelitis Optica Revealed by LC-Ag(+)CIS/MS/MS and LC-ESI/MS/MS with Picolinic Derivatization: Increased Levels and Association with Disability during Acute Attack
title_fullStr Hydroxycholesterol Levels in the Serum and Cerebrospinal Fluid of Patients with Neuromyelitis Optica Revealed by LC-Ag(+)CIS/MS/MS and LC-ESI/MS/MS with Picolinic Derivatization: Increased Levels and Association with Disability during Acute Attack
title_full_unstemmed Hydroxycholesterol Levels in the Serum and Cerebrospinal Fluid of Patients with Neuromyelitis Optica Revealed by LC-Ag(+)CIS/MS/MS and LC-ESI/MS/MS with Picolinic Derivatization: Increased Levels and Association with Disability during Acute Attack
title_short Hydroxycholesterol Levels in the Serum and Cerebrospinal Fluid of Patients with Neuromyelitis Optica Revealed by LC-Ag(+)CIS/MS/MS and LC-ESI/MS/MS with Picolinic Derivatization: Increased Levels and Association with Disability during Acute Attack
title_sort hydroxycholesterol levels in the serum and cerebrospinal fluid of patients with neuromyelitis optica revealed by lc-ag(+)cis/ms/ms and lc-esi/ms/ms with picolinic derivatization: increased levels and association with disability during acute attack
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5152860/
https://www.ncbi.nlm.nih.gov/pubmed/27942009
http://dx.doi.org/10.1371/journal.pone.0167819
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