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Novel Autoantibodies in Idiopathic Small Fiber Neuropathy
OBJECTIVE: Small fiber neuropathy (SFN) is clinically and etiologically heterogeneous. Although autoimmunity has been postulated to be pathophysiologically important in SFN, few autoantibodies have been described. We aimed to identify autoantibodies associated with idiopathic SFN (iSFN) by a novel h...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300200/ https://www.ncbi.nlm.nih.gov/pubmed/34761434 http://dx.doi.org/10.1002/ana.26268 |
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author | Chan, Amanda C. Y. Wong, Hiu Yi Chong, Yao Feng Lai, Poh San Teoh, Hock Luen Ng, Alison Y. Y. Hung, Jennifer H. M. Chan, Yee Cheun Ng, Kay W. P. Vijayan, Joy Ong, Jonathan J. Y. Chandra, Bharatendu Tan, Chi Hsien Rutt, Nurul H. Tan, Ti Myen Ismail, Nur Hafiza Wilder‐Smith, Einar Schwarz, Herbert Choi, Hyungwon Sharma, Vijay K. Mak, Anselm |
author_facet | Chan, Amanda C. Y. Wong, Hiu Yi Chong, Yao Feng Lai, Poh San Teoh, Hock Luen Ng, Alison Y. Y. Hung, Jennifer H. M. Chan, Yee Cheun Ng, Kay W. P. Vijayan, Joy Ong, Jonathan J. Y. Chandra, Bharatendu Tan, Chi Hsien Rutt, Nurul H. Tan, Ti Myen Ismail, Nur Hafiza Wilder‐Smith, Einar Schwarz, Herbert Choi, Hyungwon Sharma, Vijay K. Mak, Anselm |
author_sort | Chan, Amanda C. Y. |
collection | PubMed |
description | OBJECTIVE: Small fiber neuropathy (SFN) is clinically and etiologically heterogeneous. Although autoimmunity has been postulated to be pathophysiologically important in SFN, few autoantibodies have been described. We aimed to identify autoantibodies associated with idiopathic SFN (iSFN) by a novel high‐throughput protein microarray platform that captures autoantibodies expressed in the native conformational state. METHODS: Sera from 58 SFN patients and 20 age‐ and gender‐matched healthy controls (HCs) were screened against >1,600 immune‐related antigens. Fluorescent unit readout and postassay imaging were performed, followed by composite data normalization and protein fold change (pFC) analysis. Analysis of an independent validation cohort of 33 SFN patients against the same 20 HCs was conducted to identify reproducible proteins in both cohorts. RESULTS: Nine autoantibodies were screened with statistical significance and pFC criteria in both cohorts, with at least 50% change in serum levels. Three proteins showed consistently high fold changes in main and validation cohorts: MX1 (FC = 2.99 and 3.07, respectively, p = 0.003, q = 0.076), DBNL (FC = 2.11 and 2.16, respectively, p = 0.009, q < 0.003), and KRT8 (FC = 1.65 and 1.70, respectively, p = 0.043, q < 0.003). Further subgroup analysis into iSFN and SFN by secondary causes (secondary SFN) in the main cohort showed that MX1 is higher in iSFN compared to secondary SFN (FC = 1.61 vs 0.106, p = 0.009). INTERPRETATION: Novel autoantibodies MX1, DBNL, and KRT8 are found in iSFN. MX1 may allow diagnostic subtyping of iSFN patients. ANN NEUROL 2022;91:66–77 |
format | Online Article Text |
id | pubmed-9300200 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93002002022-07-21 Novel Autoantibodies in Idiopathic Small Fiber Neuropathy Chan, Amanda C. Y. Wong, Hiu Yi Chong, Yao Feng Lai, Poh San Teoh, Hock Luen Ng, Alison Y. Y. Hung, Jennifer H. M. Chan, Yee Cheun Ng, Kay W. P. Vijayan, Joy Ong, Jonathan J. Y. Chandra, Bharatendu Tan, Chi Hsien Rutt, Nurul H. Tan, Ti Myen Ismail, Nur Hafiza Wilder‐Smith, Einar Schwarz, Herbert Choi, Hyungwon Sharma, Vijay K. Mak, Anselm Ann Neurol Research Articles OBJECTIVE: Small fiber neuropathy (SFN) is clinically and etiologically heterogeneous. Although autoimmunity has been postulated to be pathophysiologically important in SFN, few autoantibodies have been described. We aimed to identify autoantibodies associated with idiopathic SFN (iSFN) by a novel high‐throughput protein microarray platform that captures autoantibodies expressed in the native conformational state. METHODS: Sera from 58 SFN patients and 20 age‐ and gender‐matched healthy controls (HCs) were screened against >1,600 immune‐related antigens. Fluorescent unit readout and postassay imaging were performed, followed by composite data normalization and protein fold change (pFC) analysis. Analysis of an independent validation cohort of 33 SFN patients against the same 20 HCs was conducted to identify reproducible proteins in both cohorts. RESULTS: Nine autoantibodies were screened with statistical significance and pFC criteria in both cohorts, with at least 50% change in serum levels. Three proteins showed consistently high fold changes in main and validation cohorts: MX1 (FC = 2.99 and 3.07, respectively, p = 0.003, q = 0.076), DBNL (FC = 2.11 and 2.16, respectively, p = 0.009, q < 0.003), and KRT8 (FC = 1.65 and 1.70, respectively, p = 0.043, q < 0.003). Further subgroup analysis into iSFN and SFN by secondary causes (secondary SFN) in the main cohort showed that MX1 is higher in iSFN compared to secondary SFN (FC = 1.61 vs 0.106, p = 0.009). INTERPRETATION: Novel autoantibodies MX1, DBNL, and KRT8 are found in iSFN. MX1 may allow diagnostic subtyping of iSFN patients. ANN NEUROL 2022;91:66–77 John Wiley & Sons, Inc. 2021-12-01 2022-01 /pmc/articles/PMC9300200/ /pubmed/34761434 http://dx.doi.org/10.1002/ana.26268 Text en © 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Chan, Amanda C. Y. Wong, Hiu Yi Chong, Yao Feng Lai, Poh San Teoh, Hock Luen Ng, Alison Y. Y. Hung, Jennifer H. M. Chan, Yee Cheun Ng, Kay W. P. Vijayan, Joy Ong, Jonathan J. Y. Chandra, Bharatendu Tan, Chi Hsien Rutt, Nurul H. Tan, Ti Myen Ismail, Nur Hafiza Wilder‐Smith, Einar Schwarz, Herbert Choi, Hyungwon Sharma, Vijay K. Mak, Anselm Novel Autoantibodies in Idiopathic Small Fiber Neuropathy |
title | Novel Autoantibodies in Idiopathic Small Fiber Neuropathy |
title_full | Novel Autoantibodies in Idiopathic Small Fiber Neuropathy |
title_fullStr | Novel Autoantibodies in Idiopathic Small Fiber Neuropathy |
title_full_unstemmed | Novel Autoantibodies in Idiopathic Small Fiber Neuropathy |
title_short | Novel Autoantibodies in Idiopathic Small Fiber Neuropathy |
title_sort | novel autoantibodies in idiopathic small fiber neuropathy |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300200/ https://www.ncbi.nlm.nih.gov/pubmed/34761434 http://dx.doi.org/10.1002/ana.26268 |
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