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Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2–5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease...

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Autores principales: Costa, Júlia, Gromicho, Marta, Pronto-Laborinho, Ana, Almeida, Conceição, Gomes, Ricardo A., Guerreiro, Ana C. L., Oliva, Abel, Pinto, Susana, de Carvalho, Mamede
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305219/
https://www.ncbi.nlm.nih.gov/pubmed/34359293
http://dx.doi.org/10.3390/diagnostics11071210
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author Costa, Júlia
Gromicho, Marta
Pronto-Laborinho, Ana
Almeida, Conceição
Gomes, Ricardo A.
Guerreiro, Ana C. L.
Oliva, Abel
Pinto, Susana
de Carvalho, Mamede
author_facet Costa, Júlia
Gromicho, Marta
Pronto-Laborinho, Ana
Almeida, Conceição
Gomes, Ricardo A.
Guerreiro, Ana C. L.
Oliva, Abel
Pinto, Susana
de Carvalho, Mamede
author_sort Costa, Júlia
collection PubMed
description Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2–5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on, e.g., progression rate, with implications in therapeutic trials. Neurofilaments constitute already-promising markers for ALS and, recently, chitinases have emerged as novel marker targets for the disease. Here, we investigated cerebrospinal fluid (CSF) chitinases as potential markers for ALS. Chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), chitinase-3-like protein 2 (CHI3L2) and the benchmark marker phosphoneurofilament heavy chain (pNFH) were quantified by an enzyme-linked immunosorbent assay (ELISA) from the CSF of 34 ALS patients and 24 control patients with other neurological diseases. CSF was also analyzed by UHPLC-mass spectrometry. All three chitinases, as well as pNFH, were found to correlate with disease progression rate. Furthermore, CHIT1 was elevated in ALS patients with high diagnostic performance, as was pNFH. On the other hand, CHIT1 correlated with forced vital capacity (FVC). The three chitinases correlated with pNFH, indicating a relation between degeneration and neuroinflammation. In conclusion, our results supported the value of CHIT1 as a diagnostic and progression rate biomarker, and its potential as respiratory function marker. The results opened novel perspectives to explore chitinases as biomarkers and their functional relevance in ALS.
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spelling pubmed-83052192021-07-25 Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis Costa, Júlia Gromicho, Marta Pronto-Laborinho, Ana Almeida, Conceição Gomes, Ricardo A. Guerreiro, Ana C. L. Oliva, Abel Pinto, Susana de Carvalho, Mamede Diagnostics (Basel) Article Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2–5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on, e.g., progression rate, with implications in therapeutic trials. Neurofilaments constitute already-promising markers for ALS and, recently, chitinases have emerged as novel marker targets for the disease. Here, we investigated cerebrospinal fluid (CSF) chitinases as potential markers for ALS. Chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), chitinase-3-like protein 2 (CHI3L2) and the benchmark marker phosphoneurofilament heavy chain (pNFH) were quantified by an enzyme-linked immunosorbent assay (ELISA) from the CSF of 34 ALS patients and 24 control patients with other neurological diseases. CSF was also analyzed by UHPLC-mass spectrometry. All three chitinases, as well as pNFH, were found to correlate with disease progression rate. Furthermore, CHIT1 was elevated in ALS patients with high diagnostic performance, as was pNFH. On the other hand, CHIT1 correlated with forced vital capacity (FVC). The three chitinases correlated with pNFH, indicating a relation between degeneration and neuroinflammation. In conclusion, our results supported the value of CHIT1 as a diagnostic and progression rate biomarker, and its potential as respiratory function marker. The results opened novel perspectives to explore chitinases as biomarkers and their functional relevance in ALS. MDPI 2021-07-05 /pmc/articles/PMC8305219/ /pubmed/34359293 http://dx.doi.org/10.3390/diagnostics11071210 Text en © 2021 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
Costa, Júlia
Gromicho, Marta
Pronto-Laborinho, Ana
Almeida, Conceição
Gomes, Ricardo A.
Guerreiro, Ana C. L.
Oliva, Abel
Pinto, Susana
de Carvalho, Mamede
Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis
title Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis
title_full Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis
title_fullStr Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis
title_full_unstemmed Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis
title_short Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis
title_sort cerebrospinal fluid chitinases as biomarkers for amyotrophic lateral sclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305219/
https://www.ncbi.nlm.nih.gov/pubmed/34359293
http://dx.doi.org/10.3390/diagnostics11071210
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