Fibronectin is a serum biomarker for Duchenne muscular dystrophy.
OBJECTIVE
To identify and validate serum biomarkers for the progression of Duchenne muscular dystrophy (DMD) using a MS-based bottom-up pipeline.


METHODS
We used a bottom-up proteomics approach, including a protein concentration equalization step, different proteolytic digestions, and MS detection schemes, to identify candidate biomarkers in serum samples from control subjects and DMD patients. Fibronectin was chosen for follow-up based on the differences in peptide spectral counts and sequence coverage observed between the DMD and control groups. Subsequently, fibronectin levels were determined with ELISA in 68 DMD patients, 38 milder Becker muscular dystrophy patients, 33 patients with other neuromuscular disorders, and 15 age-matched adult and child controls.


RESULTS
There was a significant increase in fibronectin levels in DMD patients compared to age-matched controls. Fibronectin levels in patients with Becker muscular dystrophy, Bethlem myopathy, or myasthenia gravis were comparable to control levels. Progressive elevation in fibronectin levels was observed in longitudinal samples from 22 DMD patients followed up for a period of 6 months up to 4 years.


CONCLUSIONS
This study suggests that serum fibronectin levels may constitute a promising biomarker to monitor disease progression in DMD patients.
Department of Human Genetics, Leiden University Medical Center (LUMC), RC, Leiden, The Netherlands.
F
F
Cynthia Martin
Monika
M
Hiller
Pietro
P
Spitali
Stijn
S
Oonk
Hans
H
Dalebout
Magnus
M
Palmblad
Amina
A
Chaouch
Michela
M
Guglieri
Volker
V
Straub
Hanns
H
Lochmüller
Erik H
EH
Niks
Jan J G M
JJ
Verschuuren
Annemieke
A
Aartsma-Rus
André M
AM
Deelder
Yuri E M
YE
van der Burgt
Peter A C
PA
't Hoen
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003286:Contracture / Q000097:blood / Q000235:genetics / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000097:blood* / Q000235:genetics; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009136:Muscular Dystrophies / Q000097:blood / Q000151:congenital / Q000235:genetics / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000097:blood* / Q000235:genetics / Q000473:pathology; D009157:Myasthenia Gravis / Q000097:blood / Q000235:genetics / Q000473:pathology
D015415:Biomarkers; D005353:Fibronectins
Biomarker; Duchenne muscular dystrophy; Fibronectin; Spectral counting