Plasma Proteomic Analysis in Morquio A Disease
Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal disease caused by mutations in the gene encoding the enzyme<i>N</i>-acetylgalactosamine-6-sulfate sulfatase (GALNS), and is characterized by systemic skeletal dysplasia due to excessive storage of keratan sulfate (KS) and chondroiti...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/6165 |
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| author | José V. Álvarez Susana B. Bravo María Pilar Chantada-Vázquez Sofía Barbosa-Gouveia Cristóbal Colón Olalla López-Suarez Shunji Tomatsu Francisco J. Otero-Espinar María L. Couce |
| author_facet | José V. Álvarez Susana B. Bravo María Pilar Chantada-Vázquez Sofía Barbosa-Gouveia Cristóbal Colón Olalla López-Suarez Shunji Tomatsu Francisco J. Otero-Espinar María L. Couce |
| author_sort | José V. Álvarez |
| collection | DOAJ |
| description | Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal disease caused by mutations in the gene encoding the enzyme<i>N</i>-acetylgalactosamine-6-sulfate sulfatase (GALNS), and is characterized by systemic skeletal dysplasia due to excessive storage of keratan sulfate (KS) and chondroitin-6-sulfate in chondrocytes. Although improvements in the activity of daily living and endurance tests have been achieved with enzyme replacement therapy (ERT) with recombinant human GALNS, recovery of bone lesions and bone growth in MPS IVA has not been demonstrated to date. Moreover, no correlation has been described between therapeutic efficacy and urine levels of KS, which accumulates in MPS IVA patients. The objective of this study was to assess the validity of potential biomarkers proposed by other authors and to identify new biomarkers. To identify candidate biomarkers of this disease, we analyzed plasma samples from healthy controls (<i>n</i>=6) and from untreated (<i>n</i>=8) and ERT-treated (<i>n</i>=5, sampled before and after treatment) MPS IVA patients using both qualitative and quantitative proteomics analyses. The qualitative proteomics approach analyzed the proteomic profile of the different study groups. In the quantitative analysis, we identified/quantified 215 proteins after comparing healthy control untreated, ERT-treated MPSIVA patients. We selected a group of proteins that were dysregulated in MPS IVA patients. We identified four potential protein biomarkers, all of which may influence bone and cartilage metabolism: fetuin-A, vitronectin, alpha-1antitrypsin, and clusterin. Further studies of cartilage and bone samples from MPS IVA patients will be required to verify the validity of these proteins as potential biomarkers of MPS IVA. |
| first_indexed | 2024-03-10T10:37:59Z |
| format | Article |
| id | doaj.art-590948141e2d4434a5be250859edf881 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:37:59Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-590948141e2d4434a5be250859edf8812023-11-21T23:10:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012211616510.3390/ijms22116165Plasma Proteomic Analysis in Morquio A DiseaseJosé V. Álvarez0Susana B. Bravo1María Pilar Chantada-Vázquez2Sofía Barbosa-Gouveia3Cristóbal Colón4Olalla López-Suarez5Shunji Tomatsu6Francisco J. Otero-Espinar7María L. Couce8Department of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service, Health Research Institute of Santiago de Compostela (IDIS), Hospital Clínico Universitario de Santiago de Compostela, CIBERER, MetabERN, 15706 Santiago de Compostela, SpainProteomic Platform, Health Research Institute of Santiago de Compostela (IDIS), Hospital ClínicoUniversitario de Santiago de Compostela, 15706 Santiago de Compostela, SpainProteomic Platform, Health Research Institute of Santiago de Compostela (IDIS), Hospital ClínicoUniversitario de Santiago de Compostela, 15706 Santiago de Compostela, SpainHealth Research Institute of Santiago de Compostela (IDIS), CIBERER, MetabERN, 15706 Santiago de Compostela, SpainDepartment of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service, Health Research Institute of Santiago de Compostela (IDIS), Hospital Clínico Universitario de Santiago de Compostela, CIBERER, MetabERN, 15706 Santiago de Compostela, SpainDepartment of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service, Health Research Institute of Santiago de Compostela (IDIS), Hospital Clínico Universitario de Santiago de Compostela, CIBERER, MetabERN, 15706 Santiago de Compostela, SpainSkeletal Dysplasia Lab Nemours Biomedical Research Nemours/Alfred I, duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803, USAParaquasil Platform, Health Research Institute of Santiago de Compostela (IDIS), Hospital Clínico Universitario de Santiago de Compostela, 15706 Santiago de Compostela, SpainDepartment of Forensic Sciences, Pathology, Gynecology and Obstetrics, Pediatrics, Neonatology Service, Health Research Institute of Santiago de Compostela (IDIS), Hospital Clínico Universitario de Santiago de Compostela, CIBERER, MetabERN, 15706 Santiago de Compostela, SpainMucopolysaccharidosis type IVA (MPS IVA) is a lysosomal disease caused by mutations in the gene encoding the enzyme<i>N</i>-acetylgalactosamine-6-sulfate sulfatase (GALNS), and is characterized by systemic skeletal dysplasia due to excessive storage of keratan sulfate (KS) and chondroitin-6-sulfate in chondrocytes. Although improvements in the activity of daily living and endurance tests have been achieved with enzyme replacement therapy (ERT) with recombinant human GALNS, recovery of bone lesions and bone growth in MPS IVA has not been demonstrated to date. Moreover, no correlation has been described between therapeutic efficacy and urine levels of KS, which accumulates in MPS IVA patients. The objective of this study was to assess the validity of potential biomarkers proposed by other authors and to identify new biomarkers. To identify candidate biomarkers of this disease, we analyzed plasma samples from healthy controls (<i>n</i>=6) and from untreated (<i>n</i>=8) and ERT-treated (<i>n</i>=5, sampled before and after treatment) MPS IVA patients using both qualitative and quantitative proteomics analyses. The qualitative proteomics approach analyzed the proteomic profile of the different study groups. In the quantitative analysis, we identified/quantified 215 proteins after comparing healthy control untreated, ERT-treated MPSIVA patients. We selected a group of proteins that were dysregulated in MPS IVA patients. We identified four potential protein biomarkers, all of which may influence bone and cartilage metabolism: fetuin-A, vitronectin, alpha-1antitrypsin, and clusterin. Further studies of cartilage and bone samples from MPS IVA patients will be required to verify the validity of these proteins as potential biomarkers of MPS IVA.https://www.mdpi.com/1422-0067/22/11/6165biomarkersenzyme replacement therapylysosomal disordersproteomics |
| spellingShingle | José V. Álvarez Susana B. Bravo María Pilar Chantada-Vázquez Sofía Barbosa-Gouveia Cristóbal Colón Olalla López-Suarez Shunji Tomatsu Francisco J. Otero-Espinar María L. Couce Plasma Proteomic Analysis in Morquio A Disease International Journal of Molecular Sciences biomarkers enzyme replacement therapy lysosomal disorders proteomics |
| title | Plasma Proteomic Analysis in Morquio A Disease |
| title_full | Plasma Proteomic Analysis in Morquio A Disease |
| title_fullStr | Plasma Proteomic Analysis in Morquio A Disease |
| title_full_unstemmed | Plasma Proteomic Analysis in Morquio A Disease |
| title_short | Plasma Proteomic Analysis in Morquio A Disease |
| title_sort | plasma proteomic analysis in morquio a disease |
| topic | biomarkers enzyme replacement therapy lysosomal disorders proteomics |
| url | https://www.mdpi.com/1422-0067/22/11/6165 |
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