Novel Auto-antibodies in Idiopathic Small Fiber Neuropathy.

OBJECTIVE Small fiber neuropathy (SFN) is clinically and etiologically heterogeneous. While 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 native conformational state. METHODS Sera from 58 SFN patients and 20 age- and gender-matched healthy controls (HC) were screened against more than 1,600 immune-related antigens. Fluorescent unit readout and post-assay 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 HC 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, p = 0.003 and q = 0.076 respectively), DBNL (FC = 2.11 and 2.16, p =0.009 and q = <0.003 respectively), and KRT8 (FC = 1.65 and 1.70, p = 0.043 and q <0.003 respectively). Further subgroup analysis into iSFN and secondary causes of SFN (sSFN) in the main cohort showed that MX1 is higher in iSFN compared to sSFN (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. This article is protected by copyright. All rights reserved.