{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:11:27Z","timestamp":1792033887258,"version":"4.4.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/Y001826\/1"],"award-info":[{"award-number":["MR\/Y001826\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000627","name":"Guarantors of Brain","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000627","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Christos Lazari Foundation"},{"DOI":"10.13039\/100012936","name":"GBS-CIDP Foundation International","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012936","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University College London Hospitals NHS Foundation Trust Biomedical Research Centre"},{"name":"University College London Hospitals NHS Foundation Trust Biomedical Research Centre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Assessing disease progression and informing clinical trials in peripheral neuropathy would benefit from objective and responsive fluid biomarkers closely linked to disease biology. This is particularly important in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain\u2013Barr\u00e9 syndrome (GBS), the most common inflammatory neuropathies, where reliable biomarkers of peripheral demyelination would help identify, and potentially measure, active disease and responses to treatment. We postulated that periaxin, a protein exclusively expressed by myelinating Schwann cells, could serve as a fluid biomarker of demyelinating peripheral neuropathy.<\/jats:p>\n                  <jats:p>We developed a single molecule array (Simoa)-based immunoassay to measure plasma periaxin in patients with CIDP (n = 45, including longitudinal samples across a discovery cohort and a validation cohort, for a total of 77 time points), GBS (n = 30, 66 time points), Charcot\u2013Marie\u2013Tooth disease (CMT, n = 20), CNS disease controls with multiple sclerosis (n = 30) and healthy controls (n = 30). We also evaluated whether periaxin is released in myelinating co-cultures following immune-mediated demyelination and axonal damage, comparing results with uninjured cultures.<\/jats:p>\n                  <jats:p>Plasma periaxin effectively distinguishes peripheral from CNS diseases, with significantly elevated levels in CIDP, GBS and CMT, but not in CNS disease or healthy controls (all P &amp;lt; 0.01). In CIDP, periaxin discriminates patients with active disease from those with inactive disease (P &amp;lt; 0.0001), and plasma levels decrease following treatment with intravenous immunoglobulin (IVIg). Elevated periaxin strongly predicts clinical worsening at 1 year [sensitivity 99%, specificity 72%, area under the curve (AUC) 0.86 (95% confidence interval, CI: 0.67\u20131)]. In GBS, peak levels of plasma periaxin and the ratio of periaxin to axonal biomarkers [neurofilament light chain (NfL) and peripherin] discriminate most cases of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) from acute motor axonal neuropathy (AMAN), as classified by electrophysiology (sensitivity 100%, specificity 86%, AUC = 0.94, 95% CI: 0.81\u20131). Serial measurements showed that plasma periaxin levels peak 2 to 3 weeks after GBS symptom onset, followed by a gradual decline in the weeks thereafter. In vitro, periaxin is higher following immune-mediated demyelination compared with axonal damage and control conditions.<\/jats:p>\n                  <jats:p>Plasma periaxin is a biomarker of peripheral nerve demyelination. Combined with axonal fluid biomarkers and existing clinical scales, periaxin has the potential to improve the clinical management of peripheral neuropathies, accelerating advances in care and experimental research.<\/jats:p>","DOI":"10.1093\/brain\/awaf234","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T07:57:34Z","timestamp":1750406254000},"page":"4448-4460","source":"Crossref","is-referenced-by-count":18,"title":["Plasma periaxin is a biomarker of peripheral nerve demyelination"],"prefix":"10.1093","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4543-0162","authenticated-orcid":false,"given":"Roberto","family":"Bellanti","sequence":"first","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]},{"name":"Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London , London WC1N 3BG ,","place":["UK"]},{"name":"Neuroimmunology and CSF Laboratory, National Hospital for Neurology and Neurosurgery , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan Y S","family":"Keh","sequence":"additional","affiliation":[{"name":"Manchester Centre for Clinical Neurosciences, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust , Manchester M6 8HD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2102-6053","authenticated-orcid":false,"given":"Stephen","family":"Keddie","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, The Royal London Hospital, Barts Health NHS Trust , London E1 1BB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K L","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London , London WC1N 3BG ,","place":["UK"]},{"name":"Neuroimmunology and CSF Laboratory, National Hospital for Neurology and Neurosurgery , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya","family":"Misheva","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan","family":"Smyth","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9237-5878","authenticated-orcid":false,"given":"Georgios","family":"Baskozos","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaminie","family":"Moodley","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of KwaZulu-Natal , Durban 4041 ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie S","family":"Hart","sequence":"additional","affiliation":[{"name":"Neuroimmunology and CSF Laboratory, National Hospital for Neurology and Neurosurgery , London WC1N 3BG ,","place":["UK"]},{"name":"Department of Neuroinflammation, Queen Square Institute of Neurology, University College London , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J","family":"Davies","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0686-905X","authenticated-orcid":false,"given":"Mary M","family":"Reilly","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London , London WC1N 3BG ,","place":["UK"]},{"name":"Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3174-6027","authenticated-orcid":false,"given":"Michael P","family":"Lunn","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, 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