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Peripherin is a biomarker of axonal damage in peripheral nervous system disease

Keddie, Stephen; Smyth, Duncan; Keh, Ryan YS; Chou, Michael KL; Grant, Donna; Surana, Sunaina; Heslegrave, Amanda; ... Lunn, Michael P; + view all (2023) Peripherin is a biomarker of axonal damage in peripheral nervous system disease. Brain 10.1093/brain/awad234. (In press). Green open access

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Abstract

Valid, responsive blood biomarkers specific to peripheral nerve damage would improve management of peripheral nervous system (PNS) diseases. Neurofilament light chain (NfL) is sensitive for detecting axonal pathology but is not specific to PNS damage, as it is expressed throughout the PNS and central nervous system (CNS). Peripherin, another intermediate filament protein, is almost exclusively expressed in peripheral nerve axons. We postulated that peripherin would be a promising blood biomarker of PNS axonal damage. We demonstrated that peripherin is distributed in sciatic nerve, and to a lesser extent spinal cord tissue lysates, but not in brain or extra-neural tissues. In the spinal cord, anti-peripherin antibody bound only to the primary cells of the periphery (anterior horn cells, motor axons and primary afferent sensory axons). In vitro models of antibody-mediated axonal and demyelinating nerve injury showed marked elevation of peripherin levels only in axonal damage and only a minimal rise in demyelination. We developed an immunoassay using single molecule array (Simoa) technology for the detection of serum peripherin as a biomarker for PNS axonal damage. We examined longitudinal serum peripherin and NfL concentrations in individuals with Guillain-Barré syndrome (GBS, n = 45, 179 timepoints), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 35, 70 timepoints), multiple sclerosis (MS, n = 30), dementia (as non-inflammatory CNS controls, n = 30) and healthy individuals (n = 24). Peak peripherin levels were higher in GBS than all other groups (median 18.75 pg/mL vs. < 6.98 pg/mL, p < 0.0001). Peak NfL was highest in GBS (median 220.8 pg/mL) and lowest in healthy controls (median 5.6 pg/mL), but NfL did not distinguish between CIDP (17.3 pg/mL), MS (21.5 pg/mL) and dementia (29.9 pg/mL). While peak NfL levels were higher with older age (rho=+0.39, p < 0.0001), peak peripherin levels did not vary with age. In GBS, local regression analysis of serial peripherin in the majority of individuals with 3 or more timepoints of data (16/25) displayed a rise-and-fall pattern with the highest value within the first week of initial assessment. Similar analysis of serial NfL concentrations showed a later peak at 16 days. Group analysis of serum peripherin and NfL levels in GBS and CIDP patients were not significantly associated with clinical data, but in some individuals with GBS, peripherin levels appeared to better reflect clinical outcome measure improvement. Serum peripherin is a promising new, dynamic, and specific biomarker of acute PNS axonal damage.

Type: Article
Title: Peripherin is a biomarker of axonal damage in peripheral nervous system disease
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/brain/awad234
Publisher version: https://doi.org/10.1093/brain/awad234
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Guillain-Barré syndrome, axon, biomarker, neuropathy, peripheral nervous system, peripherin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10175322
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