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.
Bibliographical noteFunding 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.
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.
© 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
- Clinical Neurology