title: Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies.
abstract: Despite the recent progress in the broad-scaled analysis of proteins in body fluids, there is still a lack in protein profiling approaches for biomarkers of rare diseases. Scarcity of samples is the main obstacle hindering attempts to apply discovery driven protein profiling in rare diseases. We addressed this challenge by combining samples collected within the BIO-NMD consortium from four geographically dispersed clinical sites to identify protein markers associated with muscular dystrophy using an antibody bead array platform with 384 antibodies. Based on concordance in statistical significance and confirmatory results obtained from analysis of both serum and plasma, we identified eleven proteins associated with muscular dystrophy, among which four proteins were elevated in blood from muscular dystrophy patients: carbonic anhydrase III (CA3) and myosin light chain 3 (MYL3), both specifically expressed in slow-twitch muscle fibers and mitochondrial malate dehydrogenase 2 (MDH2) and electron transfer flavoprotein A (ETFA). Using age-matched sub-cohorts, 9 protein profiles correlating with disease progression and severity were identified, which hold promise for the development of new clinical tools for management of dystrophinopathies.
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Burcu
authors.initials: B
authors.lastname: Ayoglu
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Amina
authors.initials: A
authors.lastname: Chaouch
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.affiliation: Cardiomiology and Medical Genetics, Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Politano
authors.affiliation: Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesú Children's Hospital, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Pietro
authors.initials: P
authors.lastname: Spitali
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Monika
authors.initials: M
authors.lastname: Hiller
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Eric H
authors.initials: EH
authors.lastname: Niks
authors.affiliation: Unit of Medical Genetics, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gualandi
authors.affiliation: SciLifeLab, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Aartsma-Rus
authors.affiliation: Ariadne Diagnostics, Rockville, MD, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Schwartz
authors.affiliation: Elsevier, Amsterdam, The Netherlands.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Priol
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.affiliation: Research Center for Genetic Medicine, Childrens National Medical Center, Washington, DC, USA.
authors.forename: Sebahattin
authors.initials: S
authors.lastname: Cirak
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Peter A C
authors.initials: PA
authors.lastname: 't Hoen
authors.affiliation: The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.affiliation: Unit of Medical Genetics, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferlini
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Jochen M
authors.initials: JM
authors.lastname: Schwenk
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.affiliation: Department of Proteomics, School of Biotechnology KTH-Royal Institute of Technology, Stockholm, Sweden caks@kth.se.
authors.forename: Cristina
authors.initials: C
authors.lastname: Al-Khalili Szigyarto
mesh_terms: D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000097:blood* / Q000175:diagnosis; D040081:Protein Array Analysis / Q000379:methods; D040901:Proteomics / Q000379:methods; D035583:Rare Diseases / Q000097:blood / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D001798:Blood Proteins
keywords: Duchenne muscular dystrophy; antibody‐based proteomics; disease severity biomarkers; plasma profilling; protein profiling