title: Comparative mass spectrometric and immunoassay-based proteome analysis in serum of Duchenne muscular dystrophy patients.
abstract: OBJECTIVE
  Duchenne muscular dystrophy (DMD) is a severe and fatal neuromuscular disease. With the current developments on novel therapeutic strategies for DMD, the need to carefully monitor disease progression or regression upon treatment using molecular markers has become urgent.
  
  
  METHODS
  2D LC protein fractionation was performed on patient serum samples, followed by LC-MS/MS-based identifications with label-free quantifications.
  
  
  RESULTS
  Protein signatures were compared between patients and healthy (child and adult) controls and between ambulant and nonambulant patients. Various myofibrillar proteins demonstrated differences between DMD patients and controls, likely due to leakiness and breakdown of muscle fibers. Previously reported biomarkers, such as muscle-derived titin, myosin, and carbonic anhydrase I (CA1), were verified. MS-based results were compared with ELISA for vitamin D binding protein (GC), fibulin-1 (FBLN1), gelsolin (GSN), and carbonic anhydrase 1 (CA1).
  
  
  CONCLUSIONS
  The combined results of MS- and ELISA-based quantifications indicated more studies are needed to validate this serum protein signature for DMD patients. With these data promising candidate biomarkers have been identified for a rare genetic disease using serum proteome analysis.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Stijn
authors.initials: S
authors.lastname: Oonk
authors.affiliation: Department of Human Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Pietro
authors.initials: P
authors.lastname: Spitali
authors.affiliation: Department of Human Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Monika
authors.initials: M
authors.lastname: Hiller
authors.affiliation: Department of Human Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.|Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: Switzar
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Dalebout
authors.affiliation: John Walton Muscular Dystrophy Research Center, International Centre for Life, Central Parkway, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Mattia
authors.initials: M
authors.lastname: Calissano
authors.affiliation: John Walton Muscular Dystrophy Research Center, International Centre for Life, Central Parkway, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.affiliation: Department of Human Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.|John Walton Muscular Dystrophy Research Center, International Centre for Life, Central Parkway, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Aartsma-Rus
authors.affiliation: Department of Human Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Peter A C
authors.initials: PA
authors.lastname: 't Hoen
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Yuri E M
authors.initials: YE
authors.lastname: van der Burgt
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D002648:Child; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D013058:Mass Spectrometry; D020388:Muscular Dystrophy, Duchenne / Q000097:blood*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D020543:Proteome
keywords: 2D-HPLC; Biomarkers; Disease monitoring; Duchenne muscular dystrophy; LC-MALDI-MS; Serum proteomics