Intrathecal cytokine profile in neuropathy with anti-neurofascin 155 antibody

Hidenori Ogata, Xu Zhang, Ryo Yamasaki, Takayuki Fujii, Akira Machida, Nobutoshi Morimoto, Kenichi Kaida, Teruaki Masuda, Yukio Ando, Motoi Kuwahara, Susumu Kusunoki, Yuri Nakamura, Takuya Matsushita, Noriko Isobe, Jun ichi Kira

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Abstract

Objective: To characterize the CSF cytokine profile in chronic inflammatory demyelinating polyneuropathy (CIDP) patients with IgG4 anti-neurofascin 155 (NF155) antibodies (NF155+ CIDP) or those lacking anti-NF155 antibodies (NF155 CIDP). Methods: Twenty-eight CSF cytokines/chemokines/growth factors were measured by multiplexed fluorescent immunoassay in 35 patients with NF155+ CIDP, 36 with NF155 CIDP, and 28 with non-inflammatory neurological disease (NIND). Results: CSF CXCL8/IL-8, IL-13, TNF-α, CCL11/eotaxin, CCL2/MCP-1, and IFN-γ were significantly higher, while IL-1β, IL-1ra, and G-CSF were lower, in NF155+ CIDP than in NIND. Compared with NF155 CIDP, CXCL8/IL-8 and IL-13 were significantly higher, and IL-1β, IL-1ra, and IL-6 were lower, in NF155+ CIDP. CXCL8/IL-8, IL-13, CCL11/eotaxin, CXCL10/IP-10, CCL3/MIP-1α, CCL4/MIP-1β, and TNF-α levels were positively correlated with markedly elevated CSF protein, while IL-13, CCL11/eotaxin, and IL-17 levels were positively correlated with increased CSF cell counts. IL-13, CXCL8/IL-8, CCL4/MIP-1β, CCL3/MIP-1α, and CCL5/RANTES were decreased by combined immunotherapies in nine NF155+ CIDP patients examined longitudinally. By contrast, NF155 CIDP had significantly increased IFN-γ compared with NIND, and exhibited positive correlations of IFN-γ, CXCL10/IP-10, and CXCL8/IL-8 with CSF protein. Canonical discriminant analysis of cytokines/chemokines revealed that NF155+ and NF155 CIDP were separable, and that IL-4, IL-10, and IL-13 were the three most significant discriminators. Interpretation: Intrathecal upregulation of type 2 helper T (Th2) cell cytokines is characteristic of IgG4 NF155+ CIDP, while type 1 helper T cell cytokines are increased in CIDP regardless of the presence or absence of anti-NF155 antibodies, suggesting that overproduction of Th2 cell cytokines is unique to NF155+ CIDP.

Original languageEnglish
Pages (from-to)2304-2316
Number of pages13
JournalAnnals of Clinical and Translational Neurology
Volume6
Issue number11
DOIs
Publication statusPublished - Nov 1 2019

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Neurology

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    Ogata, H., Zhang, X., Yamasaki, R., Fujii, T., Machida, A., Morimoto, N., Kaida, K., Masuda, T., Ando, Y., Kuwahara, M., Kusunoki, S., Nakamura, Y., Matsushita, T., Isobe, N., & Kira, J. I. (2019). Intrathecal cytokine profile in neuropathy with anti-neurofascin 155 antibody. Annals of Clinical and Translational Neurology, 6(11), 2304-2316. https://doi.org/10.1002/acn3.50931