{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:08:30Z","timestamp":1793210910490,"version":"4.5.0"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science, Tokyo, Japan","award":["24K10621"],"award-info":[{"award-number":["24K10621"]}]},{"name":"Japan Society for the Promotion of Science, Tokyo, Japan","award":["21K07416"],"award-info":[{"award-number":["21K07416"]}]},{"name":"Japan Society for the Promotion of Science, Tokyo, Japan","award":["20H00529"],"award-info":[{"award-number":["20H00529"]}]},{"name":"research on intractable diseases (Neuroimmunological Disease Research Committee) from the Ministry of Health, Labour and Welfare of Japan"},{"name":"Chugai Foundation for Innovation Drug Discovery Science and Life Science Foundation of Japan"},{"DOI":"10.13039\/100012131","name":"Brain Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012131","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Impairment of the blood\u2013nerve barrier (BNB) is associated with the pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). This research analyzes the molecular mechanisms of immunoglobulin (Ig) G in patients with typical CIDP, CIDP variants (multifocal CIDP), and multifocal motor neuropathy in BNB-endothelial cells. IgG was purified from the sera of patients with typical CIDP (n = 15), multifocal CIDP (n = 14), multifocal motor neuropathy (MMN; n = 12), and healthy controls (HCs; n = 14). Molecular changes in the RNA-seq\/high-content imaging system and permeability were evaluated after the incubation of human peripheral nerve microvascular endothelial cells (PnMECs) with IgG. RNA-seq and a pathway analysis using PnMECs showed that TNF-\u03b1, CCL20 (MIP-3\u03b1), and ICAM-1 were the centers of the upregulated gene pathways in patients with typical CIDP. TNF-\u03b1, VCAM-1, NF-\u03baB, and CSF2 (GM-CSF) are important molecules in patients with multifocal CIDP. The high-content imaging system demonstrated that MIP-3, GM-CSF, and VCAM-1 increased after exposure to typical CIDP-IgG, claudin-5 decreased after exposure to IgG from patients with multifocal CIDP, and TNF-\u03b1 and VCAM-1 increased after exposure to IgG from patients with MMN. The 10 kDa dextran permeability using coculture with PnMECs and pericytes increased after exposure to IgG from patients with typical CIDP and multifocal CIDP. This effect was reversed after incubation with GM-CSF neutralizing antibodies. Upregulation of MIP-3, GM-CSF, and VCAM-1 may contribute to the infiltration of leukocytes\/lymphocytes\/monocytes across the BNB into the PNS in typical CIDP. IgG from typical CIDP and multifocal CIDP may decrease barrier properties through autocrine GM-CSF from PnMECs. VCAM-1 upregulation through autocrine TNF secretion in PnMECs may induce lymphocyte entry across the BNB in MMN.<\/jats:p>","DOI":"10.3390\/ijms27021088","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:16:59Z","timestamp":1769159819000},"page":"1088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Blood\u2013Nerve Barrier Breakdown Induced by Immunoglobulin G in Typical and Multifocal Chronic Inflammatory Demyelinating Polyneuropathy and Multifocal Motor Neuropathy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4163-2939","authenticated-orcid":false,"given":"Fumitaka","family":"Shimizu","sequence":"first","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3290-0754","authenticated-orcid":false,"given":"Yoichi","family":"Mizukami","sequence":"additional","affiliation":[{"name":"Center for Gene Research, Yamaguchi University, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5069-1706","authenticated-orcid":false,"given":"Kenji","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Center for Gene Research, Yamaguchi University, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonoko","family":"Misawa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"},{"name":"Department of Neurology and Neurological Science, Institute of Science, Tokyo 113-8519, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3048-9041","authenticated-orcid":false,"given":"Yuishin","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima 770-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kuwabara","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4714-3044","authenticated-orcid":false,"given":"Masayuki","family":"Nakamori","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1136\/jnnp-2019-320314","article-title":"Chronic inflammatory demyelinating polyneuropathy: Update on diagnosis, immunopathogenesis and treatment","volume":"90","author":"Lehmann","year":"2019","journal-title":"J. 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