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Antiplexin D1 Antibodies Relate to Small Fiber Neuropathy and Induce Neuropathic Pain in Animals

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Abstract
Objectives To assess the prevalence of antiplexin D1 antibodies (plexin D1-immunoglobulin G [IgG]) in small fiber neuropathy (SFN) and the effects of these antibodies in vivo. Methods We developed an ELISA for plexin D1-IgG using a recombinant extracellular domain of human plexin D1 containing the major epitope and sera from 58 subjects previously studied with a standard tissue-based indirect immunofluorescence assay (TBA). We screened 63 patients with probable SFN and 55 healthy controls (HCs) for serum plexin D1-IgG using ELISA. The results were confirmed by TBA. IgG from 3 plexin D1-IgG-positive patients, 2 plexin D1-IgG-negative inflammatory disease controls, and 2 HCs was intrathecally injected into mice, which were assessed for mechanical and thermal hypersensitivity 24 and 48 hours after injection. Results The ELISA had 75% sensitivity and 100% specificity using the TBA as a standard, and the coincidence rate of ELISA to TBA was 96.6% (56/58). The frequency of plexin D1-IgG was higher in patients with SFN than in HCs (12.7% [8/63] vs 0.0% [0/55], p = 0.007). Purified IgG from all 3 plexin D1-IgG-positive patients, but not 2 plexin D1-IgG-negative patients, induced significant mechanical and/or thermal hypersensitivity compared with IgG from HCs. In mice injected with plexin D1-IgG-positive but not D1-IgG-negative patient IgG, phosphorylated extracellular signal-regulated protein kinase immunoreactivity, an activation marker, was confined to small dorsal root ganglion neurons and was significantly more abundant than in mice injected with HC IgG. Conclusions Plexin D1-IgG is pathogenic but with low prevalence and is a potential biomarker for immunotherapy in SFN.
Author(s)
김광국이은재임영민Ayako SakodaJun-Ichi KiraKyoko IinumaRyo YamasakiTakayuki FujiiYukino Miyachi
Issued Date
2021
Type
Article
DOI
10.1212/NXI.0000000000001028
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8346
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8185707&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Antiplexin%20D1%20Antibodies%20Relate%20to%20Small%20Fiber%20Neuropathy%20and%20Induce%20Neuropathic%20Pain%20in%20Animals&offset=0&pcAvailability=true
Publisher
NEUROLOGY-NEUROIMMUNOLOGY NEUROINFLAMMATION
Location
미국
Language
영어
ISSN
2332-7812
Citation Volume
8
Citation Number
5
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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