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Technical Study of Automated High-Throughput High-Sensitive Ceruloplasmin Assay on Dried Blood Spots—Reinstate the Potential Use for Newborn Screening of Wilson Disease

In this study, we modified a fully automatic immunoassay on ceruloplasmin concentration on dried blood spots (DBS) to increase its analytical sensitivity in order to accurately differentiate newborns from true Wilson disease (WD) patients. Modifications to the assay parameters of the Roche/Hitachi C...

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Autores principales: Mak, Chloe Miu, Choi, Ching Tung, Wong, Tsz Ki, Chin, Hanson Heearn, Lai, Hillman Kai Yin, Yuet, Koon Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787923/
https://www.ncbi.nlm.nih.gov/pubmed/36547381
http://dx.doi.org/10.3390/ijns8040064
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author Mak, Chloe Miu
Choi, Ching Tung
Wong, Tsz Ki
Chin, Hanson Heearn
Lai, Hillman Kai Yin
Yuet, Koon Yu
author_facet Mak, Chloe Miu
Choi, Ching Tung
Wong, Tsz Ki
Chin, Hanson Heearn
Lai, Hillman Kai Yin
Yuet, Koon Yu
author_sort Mak, Chloe Miu
collection PubMed
description In this study, we modified a fully automatic immunoassay on ceruloplasmin concentration on dried blood spots (DBS) to increase its analytical sensitivity in order to accurately differentiate newborns from true Wilson disease (WD) patients. Modifications to the assay parameters of the Roche/Hitachi Cobas c systems immunoturbidimetric assay are adjusted to lower the limit of quantitation to 0.60 mg/L from 30 mg/L. This enables sensitive measurement of ceruloplasmin in eluent after DBS extraction. In addition, reference intervals and receiver operating characteristic curve analysis for diagnostic cut-off were established using DBS of neonates and WD adult patients. After DBS whole blood calibration, the 95th percentile of the reference interval for newborns was 86–229 mg/L. The cut-off value of 54 mg/L was found to be the most optimal point for differentiating true adult WD from newborn controls. This test shows a high area under curve of 1.000 with 100% sensitivity and specificity in differentiating normal newborns from WD adult samples. However, the results should be further validated with true newborn WD patient samples together with the consideration of other factors that can also lead to low ceruloplasmin levels. This test shows application potential in newborn screening for WD, which can save lives through early identification and timely treatment.
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spelling pubmed-97879232022-12-24 Technical Study of Automated High-Throughput High-Sensitive Ceruloplasmin Assay on Dried Blood Spots—Reinstate the Potential Use for Newborn Screening of Wilson Disease Mak, Chloe Miu Choi, Ching Tung Wong, Tsz Ki Chin, Hanson Heearn Lai, Hillman Kai Yin Yuet, Koon Yu Int J Neonatal Screen Article In this study, we modified a fully automatic immunoassay on ceruloplasmin concentration on dried blood spots (DBS) to increase its analytical sensitivity in order to accurately differentiate newborns from true Wilson disease (WD) patients. Modifications to the assay parameters of the Roche/Hitachi Cobas c systems immunoturbidimetric assay are adjusted to lower the limit of quantitation to 0.60 mg/L from 30 mg/L. This enables sensitive measurement of ceruloplasmin in eluent after DBS extraction. In addition, reference intervals and receiver operating characteristic curve analysis for diagnostic cut-off were established using DBS of neonates and WD adult patients. After DBS whole blood calibration, the 95th percentile of the reference interval for newborns was 86–229 mg/L. The cut-off value of 54 mg/L was found to be the most optimal point for differentiating true adult WD from newborn controls. This test shows a high area under curve of 1.000 with 100% sensitivity and specificity in differentiating normal newborns from WD adult samples. However, the results should be further validated with true newborn WD patient samples together with the consideration of other factors that can also lead to low ceruloplasmin levels. This test shows application potential in newborn screening for WD, which can save lives through early identification and timely treatment. MDPI 2022-12-01 /pmc/articles/PMC9787923/ /pubmed/36547381 http://dx.doi.org/10.3390/ijns8040064 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mak, Chloe Miu
Choi, Ching Tung
Wong, Tsz Ki
Chin, Hanson Heearn
Lai, Hillman Kai Yin
Yuet, Koon Yu
Technical Study of Automated High-Throughput High-Sensitive Ceruloplasmin Assay on Dried Blood Spots—Reinstate the Potential Use for Newborn Screening of Wilson Disease
title Technical Study of Automated High-Throughput High-Sensitive Ceruloplasmin Assay on Dried Blood Spots—Reinstate the Potential Use for Newborn Screening of Wilson Disease
title_full Technical Study of Automated High-Throughput High-Sensitive Ceruloplasmin Assay on Dried Blood Spots—Reinstate the Potential Use for Newborn Screening of Wilson Disease
title_fullStr Technical Study of Automated High-Throughput High-Sensitive Ceruloplasmin Assay on Dried Blood Spots—Reinstate the Potential Use for Newborn Screening of Wilson Disease
title_full_unstemmed Technical Study of Automated High-Throughput High-Sensitive Ceruloplasmin Assay on Dried Blood Spots—Reinstate the Potential Use for Newborn Screening of Wilson Disease
title_short Technical Study of Automated High-Throughput High-Sensitive Ceruloplasmin Assay on Dried Blood Spots—Reinstate the Potential Use for Newborn Screening of Wilson Disease
title_sort technical study of automated high-throughput high-sensitive ceruloplasmin assay on dried blood spots—reinstate the potential use for newborn screening of wilson disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787923/
https://www.ncbi.nlm.nih.gov/pubmed/36547381
http://dx.doi.org/10.3390/ijns8040064
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