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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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/11/7/1210 |
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| author | Júlia Costa Marta Gromicho Ana Pronto-Laborinho Conceição Almeida Ricardo A. Gomes Ana C. L. Guerreiro Abel Oliva Susana Pinto Mamede de Carvalho |
| author_facet | Júlia Costa Marta Gromicho Ana Pronto-Laborinho Conceição Almeida Ricardo A. Gomes Ana C. L. Guerreiro Abel Oliva Susana Pinto Mamede de Carvalho |
| author_sort | Júlia Costa |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T09:42:36Z |
| format | Article |
| id | doaj.art-ef931e44707d41d6ad26666a0ae421a3 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-10T09:42:36Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-ef931e44707d41d6ad26666a0ae421a32023-11-22T03:34:22ZengMDPI AGDiagnostics2075-44182021-07-01117121010.3390/diagnostics11071210Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral SclerosisJúlia Costa0Marta Gromicho1Ana Pronto-Laborinho2Conceição Almeida3Ricardo A. Gomes4Ana C. L. Guerreiro5Abel Oliva6Susana Pinto7Mamede de Carvalho8Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República, 2780-157 Oeiras, PortugalInstituto de Fisiologia, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, PortugalInstituto de Fisiologia, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, PortugalUniMS—Mass Spectrometry Unit, iBET—Instituto de Biologia Experimental e Tecnologica, 2780-157 Oeiras, PortugalUniMS—Mass Spectrometry Unit, iBET—Instituto de Biologia Experimental e Tecnologica, 2780-157 Oeiras, PortugalUniMS—Mass Spectrometry Unit, iBET—Instituto de Biologia Experimental e Tecnologica, 2780-157 Oeiras, PortugalInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República, 2780-157 Oeiras, PortugalInstituto de Fisiologia, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, PortugalInstituto de Fisiologia, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, PortugalAmyotrophic 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.https://www.mdpi.com/2075-4418/11/7/1210amyotrophic lateral sclerosischitinasescerebrospinal fluidbiomarkers |
| spellingShingle | Júlia Costa Marta Gromicho Ana Pronto-Laborinho Conceição Almeida Ricardo A. Gomes Ana C. L. Guerreiro Abel Oliva Susana Pinto Mamede de Carvalho Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis Diagnostics amyotrophic lateral sclerosis chitinases cerebrospinal fluid biomarkers |
| 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 | amyotrophic lateral sclerosis chitinases cerebrospinal fluid biomarkers |
| url | https://www.mdpi.com/2075-4418/11/7/1210 |
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