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; ... (2022). Novel Autoantibodies in Idiopathic Small Fiber Neuropathy. Annals of neurology, 91(1), pp. 66-77. Wiley-Blackwell 10.1002/ana.26268

[img]
Preview
Text
Chan__2021__Novel_Antibodies.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial (CC-BY-NC).

Download (2MB) | Preview

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 2021.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Wilder-Smith, Einar

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0364-5134

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Chantal Kottler

Date Deposited:

20 Dec 2021 11:27

Last Modified:

05 Dec 2022 15:55

Publisher DOI:

10.1002/ana.26268

PubMed ID:

34761434

BORIS DOI:

10.48350/162043

URI:

https://boris.unibe.ch/id/eprint/162043

Actions (login required)

Edit item Edit item
Provide Feedback