p75 and neural cell adhesion molecule 1 can identify pathologic Schwann cells in peripheral neuropathies

Young Hee Kim; Young Hye Kim; Yoon Kyung Shin; Young Rae Jo; Da Kyeong Park; Min Young Song; Byeol A. Yoon; Soo Hyun Nam; Jong Hyun Kim; Byung Ok Choi; Ha Young Shin; Seung Woo Kim; Se Hoon Kim; Young Bin Hong; Jong Kuk Kim; Hwan Tae Park

doi:10.1002/acn3.50828

p75 and neural cell adhesion molecule 1 can identify pathologic Schwann cells in peripheral neuropathies

Young Hee Kim, Young Hye Kim, Yoon Kyung Shin, Young Rae Jo, Da Kyeong Park, Min Young Song, Byeol A. Yoon, Soo Hyun Nam, Jong Hyun Kim, Byung Ok Choi, Ha Young Shin, Seung Woo Kim, Se Hoon Kim, Young Bin Hong, Jong Kuk Kim, Hwan Tae Park

Department of Pathology

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

Objective: Myelinated Schwann cells (SCs) in adult peripheral nerves dedifferentiate into immature cells in demyelinating neuropathies and Wallerian degeneration. This plastic SC change is actively involved in the myelin destruction and clearance as demyelinating SCs (DSCs). In inherited demyelinating neuropathy, pathologically differentiated and dysmyelinated SCs constitute the main nerve pathology. Methods: We investigated whether this SC plastic status in human neuropathic nerves could be determined by patient sera to develop disease-relevant serum biomarkers. Based on proteomics analysis of the secreted exosomes from immature SCs, we traced p75 neurotrophin receptor (p75) and neural cell adhesion molecule 1 (NCAM) in the sera of patients with peripheral neuropathy. Results: Enzyme-linked immunosorbent assay (ELISA) revealed that p75 and NCAM were subtype-specifically expressed in the sera of patients with peripheral neuropathy. In conjunction with these ELISA data, pathological analyses of animal models and human specimens suggested that the presence of DSCs in inflammatory neuropathy and of supernumerary nonmyelinating or dysmyelinating SCs in inherited neuropathy could potentially be distinguished by comparing the expression profiles of p75 and NCAM. Interpretation: This study indicates that the identification of disease-specific pathological SC stages might be a valuable tool for differential diagnosis of peripheral neuropathies.

Original language	English
Pages (from-to)	1292-1301
Number of pages	10
Journal	Annals of Clinical and Translational Neurology
Volume	6
Issue number	7
DOIs	https://doi.org/10.1002/acn3.50828
Publication status	Published - 2019 Jul

Bibliographical note

Funding Information:
Funding information This study was supported by grants from the National Research Foundation of Korea (NRF; 2016R1A5A2007009, 2016R1A5A2921654) and the National Institutes of Health (RO1 NS094388), USA. Authors thank the Korean Inflammatory Neuropathy Consortium (B.J. Kim, Korea University, J.Oh, Konkuk University, J.S. Bae, Hallym University, B.C. Suh, Sungkyunkwan University, K.J. Shin, Inje University, T.S. Nam, Chonnam National University, M.S. Park, Yeungnam University, S.B. Kim, Kyunghee University, J.H. Min, Sungkyunkwan University, S.I. Oh, Inje University, S.Y. Huh, Kosin University, J.E. Kim, Seoul Medical Center, H.Y. Seok, Keimyung University, J.M. Seok, Soonchunhyang University, S.H. Baek, Korea University) for supporting clinical data and serum specimen of patients.

Funding Information:
This study was supported by grants from the National Research Foundation of Korea (NRF; 2016R1A5A2007009, 2016R1A5A2921654) and the National Institutes of Health (RO1 NS094388), USA.

Publisher Copyright:
© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

All Science Journal Classification (ASJC) codes

Neuroscience(all)
Clinical Neurology

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Kim, Y. H., Kim, Y. H., Shin, Y. K., Jo, Y. R., Park, D. K., Song, M. Y., Yoon, B. A., Nam, S. H., Kim, J. H., Choi, B. O., Shin, H. Y., Kim, S. W., Kim, S. H., Hong, Y. B., Kim, J. K., & Park, H. T. (2019). p75 and neural cell adhesion molecule 1 can identify pathologic Schwann cells in peripheral neuropathies. Annals of Clinical and Translational Neurology, 6(7), 1292-1301. https://doi.org/10.1002/acn3.50828

@article{56551f1c40e541c2af6aaac030e3e69f,

title = "p75 and neural cell adhesion molecule 1 can identify pathologic Schwann cells in peripheral neuropathies",

abstract = "Objective: Myelinated Schwann cells (SCs) in adult peripheral nerves dedifferentiate into immature cells in demyelinating neuropathies and Wallerian degeneration. This plastic SC change is actively involved in the myelin destruction and clearance as demyelinating SCs (DSCs). In inherited demyelinating neuropathy, pathologically differentiated and dysmyelinated SCs constitute the main nerve pathology. Methods: We investigated whether this SC plastic status in human neuropathic nerves could be determined by patient sera to develop disease-relevant serum biomarkers. Based on proteomics analysis of the secreted exosomes from immature SCs, we traced p75 neurotrophin receptor (p75) and neural cell adhesion molecule 1 (NCAM) in the sera of patients with peripheral neuropathy. Results: Enzyme-linked immunosorbent assay (ELISA) revealed that p75 and NCAM were subtype-specifically expressed in the sera of patients with peripheral neuropathy. In conjunction with these ELISA data, pathological analyses of animal models and human specimens suggested that the presence of DSCs in inflammatory neuropathy and of supernumerary nonmyelinating or dysmyelinating SCs in inherited neuropathy could potentially be distinguished by comparing the expression profiles of p75 and NCAM. Interpretation: This study indicates that the identification of disease-specific pathological SC stages might be a valuable tool for differential diagnosis of peripheral neuropathies.",

author = "Kim, {Young Hee} and Kim, {Young Hye} and Shin, {Yoon Kyung} and Jo, {Young Rae} and Park, {Da Kyeong} and Song, {Min Young} and Yoon, {Byeol A.} and Nam, {Soo Hyun} and Kim, {Jong Hyun} and Choi, {Byung Ok} and Shin, {Ha Young} and Kim, {Seung Woo} and Kim, {Se Hoon} and Hong, {Young Bin} and Kim, {Jong Kuk} and Park, {Hwan Tae}",

note = "Funding Information: Funding information This study was supported by grants from the National Research Foundation of Korea (NRF; 2016R1A5A2007009, 2016R1A5A2921654) and the National Institutes of Health (RO1 NS094388), USA. Authors thank the Korean Inflammatory Neuropathy Consortium (B.J. Kim, Korea University, J.Oh, Konkuk University, J.S. Bae, Hallym University, B.C. Suh, Sungkyunkwan University, K.J. Shin, Inje University, T.S. Nam, Chonnam National University, M.S. Park, Yeungnam University, S.B. Kim, Kyunghee University, J.H. Min, Sungkyunkwan University, S.I. Oh, Inje University, S.Y. Huh, Kosin University, J.E. Kim, Seoul Medical Center, H.Y. Seok, Keimyung University, J.M. Seok, Soonchunhyang University, S.H. Baek, Korea University) for supporting clinical data and serum specimen of patients. Funding Information: This study was supported by grants from the National Research Foundation of Korea (NRF; 2016R1A5A2007009, 2016R1A5A2921654) and the National Institutes of Health (RO1 NS094388), USA. Publisher Copyright: {\textcopyright} 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.",

year = "2019",

month = jul,

doi = "10.1002/acn3.50828",

language = "English",

volume = "6",

pages = "1292--1301",

journal = "Annals of Clinical and Translational Neurology",

issn = "2328-9503",

publisher = "John Wiley and Sons Ltd",

number = "7",

}

Kim, YH, Kim, YH, Shin, YK, Jo, YR, Park, DK, Song, MY, Yoon, BA, Nam, SH, Kim, JH, Choi, BO, Shin, HY, Kim, SW, Kim, SH, Hong, YB, Kim, JK & Park, HT 2019, 'p75 and neural cell adhesion molecule 1 can identify pathologic Schwann cells in peripheral neuropathies', Annals of Clinical and Translational Neurology, vol. 6, no. 7, pp. 1292-1301. https://doi.org/10.1002/acn3.50828

TY - JOUR

T1 - p75 and neural cell adhesion molecule 1 can identify pathologic Schwann cells in peripheral neuropathies

AU - Kim, Young Hee

AU - Kim, Young Hye

AU - Shin, Yoon Kyung

AU - Jo, Young Rae

AU - Park, Da Kyeong

AU - Song, Min Young

AU - Yoon, Byeol A.

AU - Nam, Soo Hyun

AU - Kim, Jong Hyun

AU - Choi, Byung Ok

AU - Shin, Ha Young

AU - Kim, Seung Woo

AU - Kim, Se Hoon

AU - Hong, Young Bin

AU - Kim, Jong Kuk

AU - Park, Hwan Tae

N1 - Funding Information: Funding information This study was supported by grants from the National Research Foundation of Korea (NRF; 2016R1A5A2007009, 2016R1A5A2921654) and the National Institutes of Health (RO1 NS094388), USA. Authors thank the Korean Inflammatory Neuropathy Consortium (B.J. Kim, Korea University, J.Oh, Konkuk University, J.S. Bae, Hallym University, B.C. Suh, Sungkyunkwan University, K.J. Shin, Inje University, T.S. Nam, Chonnam National University, M.S. Park, Yeungnam University, S.B. Kim, Kyunghee University, J.H. Min, Sungkyunkwan University, S.I. Oh, Inje University, S.Y. Huh, Kosin University, J.E. Kim, Seoul Medical Center, H.Y. Seok, Keimyung University, J.M. Seok, Soonchunhyang University, S.H. Baek, Korea University) for supporting clinical data and serum specimen of patients. Funding Information: This study was supported by grants from the National Research Foundation of Korea (NRF; 2016R1A5A2007009, 2016R1A5A2921654) and the National Institutes of Health (RO1 NS094388), USA. Publisher Copyright: © 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.

PY - 2019/7

Y1 - 2019/7

N2 - Objective: Myelinated Schwann cells (SCs) in adult peripheral nerves dedifferentiate into immature cells in demyelinating neuropathies and Wallerian degeneration. This plastic SC change is actively involved in the myelin destruction and clearance as demyelinating SCs (DSCs). In inherited demyelinating neuropathy, pathologically differentiated and dysmyelinated SCs constitute the main nerve pathology. Methods: We investigated whether this SC plastic status in human neuropathic nerves could be determined by patient sera to develop disease-relevant serum biomarkers. Based on proteomics analysis of the secreted exosomes from immature SCs, we traced p75 neurotrophin receptor (p75) and neural cell adhesion molecule 1 (NCAM) in the sera of patients with peripheral neuropathy. Results: Enzyme-linked immunosorbent assay (ELISA) revealed that p75 and NCAM were subtype-specifically expressed in the sera of patients with peripheral neuropathy. In conjunction with these ELISA data, pathological analyses of animal models and human specimens suggested that the presence of DSCs in inflammatory neuropathy and of supernumerary nonmyelinating or dysmyelinating SCs in inherited neuropathy could potentially be distinguished by comparing the expression profiles of p75 and NCAM. Interpretation: This study indicates that the identification of disease-specific pathological SC stages might be a valuable tool for differential diagnosis of peripheral neuropathies.

AB - Objective: Myelinated Schwann cells (SCs) in adult peripheral nerves dedifferentiate into immature cells in demyelinating neuropathies and Wallerian degeneration. This plastic SC change is actively involved in the myelin destruction and clearance as demyelinating SCs (DSCs). In inherited demyelinating neuropathy, pathologically differentiated and dysmyelinated SCs constitute the main nerve pathology. Methods: We investigated whether this SC plastic status in human neuropathic nerves could be determined by patient sera to develop disease-relevant serum biomarkers. Based on proteomics analysis of the secreted exosomes from immature SCs, we traced p75 neurotrophin receptor (p75) and neural cell adhesion molecule 1 (NCAM) in the sera of patients with peripheral neuropathy. Results: Enzyme-linked immunosorbent assay (ELISA) revealed that p75 and NCAM were subtype-specifically expressed in the sera of patients with peripheral neuropathy. In conjunction with these ELISA data, pathological analyses of animal models and human specimens suggested that the presence of DSCs in inflammatory neuropathy and of supernumerary nonmyelinating or dysmyelinating SCs in inherited neuropathy could potentially be distinguished by comparing the expression profiles of p75 and NCAM. Interpretation: This study indicates that the identification of disease-specific pathological SC stages might be a valuable tool for differential diagnosis of peripheral neuropathies.

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EP - 1301

JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

IS - 7

ER -

p75 and neural cell adhesion molecule 1 can identify pathologic Schwann cells in peripheral neuropathies

Abstract

Bibliographical note

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UN SDGs

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