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 hi...

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Published in:	Annals of neurology Vol. 91; no. 1; pp. 66 - 77
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	Hoboken, USA John Wiley & Sons, Inc 01-01-2022 Wiley Subscription Services, Inc
Subjects:	Adult Aged Antigens Autoantibodies Autoantibodies - blood Autoantibodies - immunology Autoantigens - immunology Autoimmunity Cohort Studies Etiology Female Fluorescence Humans Keratin-8 - immunology Male Microfilament Proteins - immunology Middle Aged Myxovirus Resistance Proteins - immunology Neuropathy Protein arrays Protein folding Proteins Serum levels Small Fiber Neuropathy - blood Small Fiber Neuropathy - immunology src Homology Domains - immunology Subgroups
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Summary:	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
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Correction added on December 3, 2021, after first online publication: The affiliation for Einar Wilder‐Smith has been updated.
ISSN:	0364-5134 1531-8249
DOI:	10.1002/ana.26268