{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T20:11:47Z","timestamp":1773951107594,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012041","name":"Versus Arthritis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000323","name":"Pain Relief Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>To develop a standardised, automated protocol for detecting protein gene product 9.5 (PGP9.5) positive intra\u2010epidermal nerve fibres (IENFs) in skin biopsies, transitioning from the established manual technique to an automated platform. This automated method, although currently intended for research applications, may improve the accessibility of this diagnostic test for small fibre neuropathy in clinical settings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Skin biopsies (<jats:italic>n<\/jats:italic>\u2009=\u2009274) from 100 participants (fibromyalgia syndrome <jats:italic>n<\/jats:italic>\u2009=\u200962; idiopathic small fibre neuropathy: <jats:italic>n<\/jats:italic>\u2009=\u200916; healthy volunteers: <jats:italic>n<\/jats:italic>\u2009=\u200922) were processed using an automated immunohistochemistry platform. IENF quantification was performed by blinded examiners, with reliability assessed via a two\u2010way mixed\u2010effects model to evaluate inter\u2010 and intra\u2010observer variability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The automated staining system reproduced intra\u2010epidermal nerve fibre density (IENFD) counts consistent with free\u2010floating sections (mean\u2009\u00b1\u2009standard deviation: free\u2010floating: 5.6\u2009\u00b1\u20093.4 fibres\/mm; automated: 5.9\u2009\u00b1\u20093.2 fibres\/mm). A median difference of 0.3 with a lower bound 95% Confidence Interval (CI) at \u22120.00005 established non\u2010inferiority against a margin of \u22120.4 (<jats:italic>p<\/jats:italic>\u2009=\u2009.08). Specifically, the inter\u2010class correlation coefficient (class denotes consistency in measured observations) was 99% (95% CI: 0.9\u20131), indicating excellent agreement between free\u2010floating and automated methods. The inter\u2010 and intra\u2010class coefficient between examiners were both 99% (95% CI: 0.9\u20130.1) for IENFD, demonstrating high reliability using sections stained using the automated method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Automated immunohistochemistry provides high\u2010throughput reliable and reproducible intra\u2010epidermal nerve fibre quantification. This method, although currently proof\u2010of\u2010concept, for research use only, may be more widely deployed in histopathology laboratories to increase the adoption of IENFD assessment for the diagnosis of peripheral neuropathies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jns.12650","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:18:34Z","timestamp":1724285914000},"page":"329-338","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Automated immunohistochemistry of intra\u2010epidermal nerve fibres in skin biopsies: A proof\u2010of\u2010concept study"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7165-6918","authenticated-orcid":false,"given":"Jamie","family":"Burgess","sequence":"first","affiliation":[{"name":"Institute of Life Course and Medical Sciences University of Liverpool  Liverpool UK"},{"name":"Liverpool University Hospitals NHS 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