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New simple and quick method to analyze serum variant transthyretins: direct MALDI method for the screening of hereditary transthyretin amyloidosis

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is caused by a variant transthyretin (TTR), which is a serum protein secreted by the liver. Mass spectrometry (MS) is a useful tool that can detect variant TTRs in serum samples from patients with ATTRv amyloidosis. We previously r...

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Autores principales: Nomura, Toshiya, Ueda, Mitsuharu, Tasaki, Masayoshi, Misumi, Yohei, Masuda, Teruaki, Inoue, Yasuteru, Tsuda, Yukimoto, Okada, Masamitsu, Okazaki, Takahiro, Kanenawa, Kyosuke, Isoguchi, Aito, Nakamura, Makoto, Obayashi, Konen, Shinriki, Satoru, Matsui, Hirotaka, Yamashita, Taro, Ando, Yukio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537225/
https://www.ncbi.nlm.nih.gov/pubmed/31133063
http://dx.doi.org/10.1186/s13023-019-1100-y
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author Nomura, Toshiya
Ueda, Mitsuharu
Tasaki, Masayoshi
Misumi, Yohei
Masuda, Teruaki
Inoue, Yasuteru
Tsuda, Yukimoto
Okada, Masamitsu
Okazaki, Takahiro
Kanenawa, Kyosuke
Isoguchi, Aito
Nakamura, Makoto
Obayashi, Konen
Shinriki, Satoru
Matsui, Hirotaka
Yamashita, Taro
Ando, Yukio
author_facet Nomura, Toshiya
Ueda, Mitsuharu
Tasaki, Masayoshi
Misumi, Yohei
Masuda, Teruaki
Inoue, Yasuteru
Tsuda, Yukimoto
Okada, Masamitsu
Okazaki, Takahiro
Kanenawa, Kyosuke
Isoguchi, Aito
Nakamura, Makoto
Obayashi, Konen
Shinriki, Satoru
Matsui, Hirotaka
Yamashita, Taro
Ando, Yukio
author_sort Nomura, Toshiya
collection PubMed
description BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is caused by a variant transthyretin (TTR), which is a serum protein secreted by the liver. Mass spectrometry (MS) is a useful tool that can detect variant TTRs in serum samples from patients with ATTRv amyloidosis. We previously reported several mass spectrometric methods to detect variant TTRs in serum samples. Those methods require cumbersome immunoprecipitation with anti-TTR antibodies and significant time to analyze the variant TTRs. In our study here, we developed a new simple and quick method to detect variant TTRs in serum samples by means of matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) MS without immunoprecipitation (direct MALDI). METHODS: By using direct MALDI, we analyzed 288 serum samples obtained from patients who were clinically suspected having amyloidosis to investigate the usefulness of this direct MALDI method to detect variant TTRs in serum samples. RESULTS: The method completed the process within 30 min. We successfully identified variant TTRs in serum samples from patients, except for a few patients with TTR Glu61Lys and Glu89Gln mutations because of the small mass shift of those variant TTRs from wild-type TTR. We also found that the mass shifts of variant TTRs measured by direct MALDI corresponded to theoretical mass changes. CONCLUSION: Our results suggest that the direct MALDI method is useful for the screening of ATTRv amyloidosis.
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spelling pubmed-65372252019-05-30 New simple and quick method to analyze serum variant transthyretins: direct MALDI method for the screening of hereditary transthyretin amyloidosis Nomura, Toshiya Ueda, Mitsuharu Tasaki, Masayoshi Misumi, Yohei Masuda, Teruaki Inoue, Yasuteru Tsuda, Yukimoto Okada, Masamitsu Okazaki, Takahiro Kanenawa, Kyosuke Isoguchi, Aito Nakamura, Makoto Obayashi, Konen Shinriki, Satoru Matsui, Hirotaka Yamashita, Taro Ando, Yukio Orphanet J Rare Dis Research BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv amyloidosis) is caused by a variant transthyretin (TTR), which is a serum protein secreted by the liver. Mass spectrometry (MS) is a useful tool that can detect variant TTRs in serum samples from patients with ATTRv amyloidosis. We previously reported several mass spectrometric methods to detect variant TTRs in serum samples. Those methods require cumbersome immunoprecipitation with anti-TTR antibodies and significant time to analyze the variant TTRs. In our study here, we developed a new simple and quick method to detect variant TTRs in serum samples by means of matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) MS without immunoprecipitation (direct MALDI). METHODS: By using direct MALDI, we analyzed 288 serum samples obtained from patients who were clinically suspected having amyloidosis to investigate the usefulness of this direct MALDI method to detect variant TTRs in serum samples. RESULTS: The method completed the process within 30 min. We successfully identified variant TTRs in serum samples from patients, except for a few patients with TTR Glu61Lys and Glu89Gln mutations because of the small mass shift of those variant TTRs from wild-type TTR. We also found that the mass shifts of variant TTRs measured by direct MALDI corresponded to theoretical mass changes. CONCLUSION: Our results suggest that the direct MALDI method is useful for the screening of ATTRv amyloidosis. BioMed Central 2019-05-27 /pmc/articles/PMC6537225/ /pubmed/31133063 http://dx.doi.org/10.1186/s13023-019-1100-y Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Nomura, Toshiya
Ueda, Mitsuharu
Tasaki, Masayoshi
Misumi, Yohei
Masuda, Teruaki
Inoue, Yasuteru
Tsuda, Yukimoto
Okada, Masamitsu
Okazaki, Takahiro
Kanenawa, Kyosuke
Isoguchi, Aito
Nakamura, Makoto
Obayashi, Konen
Shinriki, Satoru
Matsui, Hirotaka
Yamashita, Taro
Ando, Yukio
New simple and quick method to analyze serum variant transthyretins: direct MALDI method for the screening of hereditary transthyretin amyloidosis
title New simple and quick method to analyze serum variant transthyretins: direct MALDI method for the screening of hereditary transthyretin amyloidosis
title_full New simple and quick method to analyze serum variant transthyretins: direct MALDI method for the screening of hereditary transthyretin amyloidosis
title_fullStr New simple and quick method to analyze serum variant transthyretins: direct MALDI method for the screening of hereditary transthyretin amyloidosis
title_full_unstemmed New simple and quick method to analyze serum variant transthyretins: direct MALDI method for the screening of hereditary transthyretin amyloidosis
title_short New simple and quick method to analyze serum variant transthyretins: direct MALDI method for the screening of hereditary transthyretin amyloidosis
title_sort new simple and quick method to analyze serum variant transthyretins: direct maldi method for the screening of hereditary transthyretin amyloidosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537225/
https://www.ncbi.nlm.nih.gov/pubmed/31133063
http://dx.doi.org/10.1186/s13023-019-1100-y
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