{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:45:16Z","timestamp":1791485116312,"version":"4.3.4"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The envelope proteins syncytin-1 and pHERV-W from the Human Endogenous Retroviral family \u2018W\u2019 (HERV-W) have been identified as potential risk factors in multiple sclerosis (MS). This study aims to evaluate both humoral and cell-mediated immune response to antigenic peptides derived from these proteins across different clinical forms and inflammatory phases of MS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Indirect enzyme-linked immunosorbent assay (ELISA) was employed to measure immunoglobulin G (IgG) responses to syncytin-1<jats:sub>env 486-500<\/jats:sub> and pHERV-W<jats:sub>env 486-504<\/jats:sub> peptides in MS patients. Discriminant analysis was used to assess whether clinical course prediction could be enhanced by integrating clinical variables with humoral response data against other MS-associated viral factors. Additionally, peripheral blood mononuclear cells from MS patients and healthy controls (HC) were analyzed for inflammatory responses following stimulation with these peptides.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MS patients exhibited significantly elevated antibody titers against -pHERV-W<jats:sub>env 486-504<\/jats:sub> and syncytin-1<jats:sub>env 486-500<\/jats:sub> compared to HCs, with the highest levels observed in progressive MS forms. Discriminant analysis accurately predicted the clinical course in 75.3% of the cases, with an 85% accuracy rate for progressive MS. <jats:italic>In vitro<\/jats:italic>, stimulation with pHERV-W<jats:sub>env 486-504<\/jats:sub> led to a notable increase in pro-inflammatory cytokine production by CD4, CD8, and CD19 cells compared to syncytin-1<jats:sub>env 486-500<\/jats:sub>. <jats:sub>A<\/jats:sub> strong correlation was found between pHERV- W<jats:sub>env 486-504<\/jats:sub> induced cytokine production and EBV and CMV titers in MS patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings suggest that the pHERV-W envelope protein could be a valuable biomarker for monitoring peripheral inflammation in MS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1505239","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T05:12:21Z","timestamp":1736399541000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Immune response profiling of HERV-W envelope proteins in multiple sclerosis: potential biomarkers for disease progression"],"prefix":"10.3389","volume":"15","author":[{"given":"Stefano","family":"Ruberto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda I.","family":"Dom\u0131nguez-Mozo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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