Journal article
Transmembrane protease serine 5: a novel Schwann cell plasma marker for CMT1A
Annals of clinical and translational neurology, Vol.7(1), pp.69-82
01/2020
DOI: 10.1002/acn3.50965
PMCID: PMC6952315
PMID: 31833243
Abstract
Objective
Development of biomarkers for Charcot‐Marie‐Tooth (CMT) disease is critical for implementing effective clinical trials. The most common form of CMT, type 1A, is caused by a genomic duplication surrounding the PMP22 gene. A recent report (Neurology 2018;90:e518–3524) showed elevation of neurofilament light (NfL) in plasma of CMT1A disease patients, which correlated with disease severity. However, no plasma/serum biomarker has been identified that is specific to Schwann cells, the most directly affected cells in CMT1A.
Methods
We used the Olink immuno PCR platform to profile CMT1A patient (n = 47, 2 cohorts) and normal control plasma (n = 41, two cohorts) on five different Olink panels to screen 398 unique proteins.
Results
The TMPRSS5 protein (Transmembrane protease serine 5) was elevated 2.07‐fold (P = <0.0001) in two independent cohorts of CMT1A samples relative to controls. TMPRSS5 is most highly expressed in Schwann cells of peripheral nerve. Consistent with early myelination deficits in CMT1A, TMPRSS5 was not significantly correlated with disease score (CMTES‐R, CMTNS‐R), nerve conduction velocities (Ulnar CMAP, Ulnar MNCV), or with age. TMPRSS5 was not significantly elevated in smaller sample sets from patients with CMT2A, CMT2E, CMT1B, or CMT1X. The Olink immuno PCR assays confirmed elevated levels of NfL (average 1.58‐fold, P < 0.0001), which correlated with CMT1A patient disease score.
Interpretation
These data identify the first Schwann cell‐specific protein that is elevated in plasma of CMT1A patients, and may provide a disease marker and a potentially treatment‐responsive biomarker with good disease specificity for clinical trials.
Details
- Title: Subtitle
- Transmembrane protease serine 5: a novel Schwann cell plasma marker for CMT1A
- Creators
- Hongge Wang - SanofiXingyao Wu - University of IowaRiccardo Zuccarino - University of IowaMatthew Davison - SanofiKathryn Wang - SanofiChelsea Bacon - University of IowaMartin Kramer - SanofiYunhong Bai - University of IowaLaurie Gutmann - University of IowaKatherine Call - SanofiMichael E Shy - University of IowaJun Luo - SanofiJohn J Moran - University of WisconsinShawna M. E Feely - University of IowaTiffany Grider - University of IowaAlexander M Rossor - University College LondonMary M Reilly - University College LondonJohn Svaren - University of WisconsinTai-he Xia
- Resource Type
- Journal article
- Publication Details
- Annals of clinical and translational neurology, Vol.7(1), pp.69-82
- DOI
- 10.1002/acn3.50965
- PMID
- 31833243
- PMCID
- PMC6952315
- NLM abbreviation
- Ann Clin Transl Neurol
- ISSN
- 2328-9503
- eISSN
- 2328-9503
- Number of pages
- 14
- Grant note
- Stahl family research funds Rovner Family Neuromuscular Research Fund Charcot Marie Tooth Association NCATS National Institute of Neurological Disorders and Stroke (U54NS065712) National Center for Advancing Translational Sciences (U54NS065712) National Institute of Child Health and Human Development (U54HD090256)
- Language
- English
- Date published
- 01/2020
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984070366302771
Metrics
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