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A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease caused by pathogenic variations in the DMD gene. There is a need for robust DMD biomarkers for diagnostic screening and to aid therapy monitoring. Creatine kinase, to date, is the only routinely used blood biomarker for DMD, although...

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Autores principales: Rossi, Rachele, Johansson, Camilla, Heywood, Wendy, Vinette, Heloise, Jensen, Gabriella, Tegel, Hanna, Jiménez-Requena, Albert, Torelli, Silvia, Al-Khalili Szigyarto, Cristina, Ferlini, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049465/
https://www.ncbi.nlm.nih.gov/pubmed/36982290
http://dx.doi.org/10.3390/ijms24065215
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author Rossi, Rachele
Johansson, Camilla
Heywood, Wendy
Vinette, Heloise
Jensen, Gabriella
Tegel, Hanna
Jiménez-Requena, Albert
Torelli, Silvia
Al-Khalili Szigyarto, Cristina
Ferlini, Alessandra
author_facet Rossi, Rachele
Johansson, Camilla
Heywood, Wendy
Vinette, Heloise
Jensen, Gabriella
Tegel, Hanna
Jiménez-Requena, Albert
Torelli, Silvia
Al-Khalili Szigyarto, Cristina
Ferlini, Alessandra
author_sort Rossi, Rachele
collection PubMed
description Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease caused by pathogenic variations in the DMD gene. There is a need for robust DMD biomarkers for diagnostic screening and to aid therapy monitoring. Creatine kinase, to date, is the only routinely used blood biomarker for DMD, although it lacks specificity and does not correlate with disease severity. To fill this critical gap, we present here novel data about dystrophin protein fragments detected in human plasma by a suspension bead immunoassay using two validated anti-dystrophin-specific antibodies. Using both antibodies, a reduction of the dystrophin signal is detected in a small cohort of plasma samples from DMD patients when compared to healthy controls, female carriers, and other neuromuscular diseases. We also demonstrate the detection of dystrophin protein by an antibody-independent method using targeted liquid chromatography mass spectrometry. This last assay detects three different dystrophin peptides in all healthy individuals analysed and supports our finding that dystrophin protein is detectable in plasma. The results of our proof-of-concept study encourage further studies in larger sample cohorts to investigate the value of dystrophin protein as a low invasive blood biomarker for diagnostic screening and clinical monitoring of DMD.
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spelling pubmed-100494652023-03-29 A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring Rossi, Rachele Johansson, Camilla Heywood, Wendy Vinette, Heloise Jensen, Gabriella Tegel, Hanna Jiménez-Requena, Albert Torelli, Silvia Al-Khalili Szigyarto, Cristina Ferlini, Alessandra Int J Mol Sci Article Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease caused by pathogenic variations in the DMD gene. There is a need for robust DMD biomarkers for diagnostic screening and to aid therapy monitoring. Creatine kinase, to date, is the only routinely used blood biomarker for DMD, although it lacks specificity and does not correlate with disease severity. To fill this critical gap, we present here novel data about dystrophin protein fragments detected in human plasma by a suspension bead immunoassay using two validated anti-dystrophin-specific antibodies. Using both antibodies, a reduction of the dystrophin signal is detected in a small cohort of plasma samples from DMD patients when compared to healthy controls, female carriers, and other neuromuscular diseases. We also demonstrate the detection of dystrophin protein by an antibody-independent method using targeted liquid chromatography mass spectrometry. This last assay detects three different dystrophin peptides in all healthy individuals analysed and supports our finding that dystrophin protein is detectable in plasma. The results of our proof-of-concept study encourage further studies in larger sample cohorts to investigate the value of dystrophin protein as a low invasive blood biomarker for diagnostic screening and clinical monitoring of DMD. MDPI 2023-03-08 /pmc/articles/PMC10049465/ /pubmed/36982290 http://dx.doi.org/10.3390/ijms24065215 Text en © 2023 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
Rossi, Rachele
Johansson, Camilla
Heywood, Wendy
Vinette, Heloise
Jensen, Gabriella
Tegel, Hanna
Jiménez-Requena, Albert
Torelli, Silvia
Al-Khalili Szigyarto, Cristina
Ferlini, Alessandra
A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring
title A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring
title_full A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring
title_fullStr A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring
title_full_unstemmed A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring
title_short A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring
title_sort proof of principle proteomic study detects dystrophin in human plasma: implications in dmd diagnosis and clinical monitoring
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049465/
https://www.ncbi.nlm.nih.gov/pubmed/36982290
http://dx.doi.org/10.3390/ijms24065215
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