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

Takayuki Fujii, Eun Jae Lee, Yukino Miyachi, Ryo Yamasaki, Young Min Lim, Kyoko Iinuma, Ayako Sakoda, Kwang Kuk Kim, Jun Ichi Kira

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalNeurology(R) neuroimmunology & neuroinflammation
Volume8
Issue number5
DOIs
Publication statusPublished - Jul 1 2021

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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