{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T05:22:42Z","timestamp":1787376162533,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012427","name":"Beijing Tiantan Hospital, Capital Medical University","doi-asserted-by":"crossref","award":["2020MP08"],"award-info":[{"award-number":["2020MP08"]}],"id":[{"id":"10.13039\/501100012427","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012427","name":"Beijing Tiantan Hospital, Capital Medical University","doi-asserted-by":"crossref","award":["CS-2025-02"],"award-info":[{"award-number":["CS-2025-02"]}],"id":[{"id":"10.13039\/501100012427","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["L2510074"],"award-info":[{"award-number":["L2510074"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Diagnostic evaluation of suspected neuromyelitis optica spectrum disorder (NMOSD) integrates AQP4-IgG testing, clinical assessment, neuroimaging, and exclusion of alternative inflammatory demyelinating disorders; nevertheless, some patients remain diagnostically unresolved or may be misclassified as multiple sclerosis (MS) or other disorders. Methods: This single-center retrospective exploratory study analyzed quantitative serum proteomics from 20 patients with MS and 20 with NMOSD. Proteins meeting nominal p &lt; 0.05 together with prespecified fold-change criteria were considered exploratory candidates. VWF, PPBP, and SERPINA3 were subsequently assessed by ELISA in a separate, non-overlapping cohort from the same center, together with routine hematological variables. Results: Among 261 protein entries, 34 met the exploratory nominal threshold and fold-change criteria, but none remained significant after Benjamini\u2013Hochberg correction (lowest q = 0.0734). VWF and PPBP showed no significant differences across the four validation groups. SERPINA3 differed across groups (Kruskal\u2013Wallis H = 44.982, p = 9.34 \u00d7 10\u221210) and was higher in NMOSD than in MS, TBI, and HCs after Holm adjustment (adjusted p = 0.036, 1.49 \u00d7 10\u22129, and 1.13 \u00d7 10\u22125, respectively). In the full ELISA cohort, the AUC was 0.928 for NMOSD versus HC and 0.800 for NMOSD versus MS. In a post hoc sensitivity analysis excluding participants with preceding infection, the NMOSD\u2013MS separation was attenuated. In smaller complete-case analyses, adding an additional laboratory variable to SERPINA3 did not significantly improve apparent discrimination. Conclusions: SERPINA3 is therefore an exploratory adjunctive serum biomarker candidate rather than a stand-alone diagnostic test; prospective external validation in clinically representative cohorts is required.<\/jats:p>","DOI":"10.3390\/diagnostics16162660","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:55:18Z","timestamp":1787223318000},"page":"2660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum SERPINA3 as a Candidate Non-Invasive Biomarker for Neuromyelitis Optica Spectrum Disorder: Proteomic Discovery and Same-Center Validation"],"prefix":"10.3390","volume":"16","author":[{"given":"Ting","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"},{"name":"Laboratory Diagnosis Platform for Nervous System Infectious Diseases, Laboratory for Clinical Medicine, Capital Medical University, Beijing 100070, China"},{"name":"Beijing Key Laboratory of Biomarker Screening and Translational Research in Neurological Diseases, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6920-4480","authenticated-orcid":false,"given":"Bingqing","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"},{"name":"Laboratory Diagnosis Platform for Nervous System Infectious Diseases, Laboratory for Clinical Medicine, Capital Medical University, Beijing 100070, China"},{"name":"Beijing Key Laboratory of Biomarker Screening and Translational Research in Neurological Diseases, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"},{"name":"Laboratory Diagnosis Platform for Nervous System Infectious Diseases, Laboratory for Clinical Medicine, Capital Medical University, Beijing 100070, China"},{"name":"Beijing Key Laboratory of Biomarker Screening and Translational Research in Neurological Diseases, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"},{"name":"Laboratory Diagnosis Platform for Nervous System Infectious Diseases, Laboratory for Clinical Medicine, Capital Medical University, Beijing 100070, China"},{"name":"Beijing Key Laboratory of Biomarker Screening and Translational Research in Neurological Diseases, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Fifth Clinical Medical School, Capital Medical University, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"},{"name":"Laboratory Diagnosis Platform for Nervous System Infectious Diseases, Laboratory for Clinical Medicine, Capital Medical University, Beijing 100070, China"},{"name":"Beijing Key Laboratory of Biomarker Screening and Translational Research in Neurological Diseases, Beijing 100070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1007\/s00415-023-11634-0","article-title":"Update on the diagnosis and treatment of neuromyelits optica spectrum disorders (NMOSD)\u2014Revised recommendations of the Neuromyelitis Optica Study Group (NEMOS). 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