{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T06:03:07Z","timestamp":1774245787987,"version":"3.50.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Serum biomarkers of multiple sclerosis (MS), such as glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL), are established indicators of disease progression and disability. Human endogenous retrovirus of the W family (HERV-W) is repeatedly associated with MS neuroinflammation, but its relationship with neural injury biomarkers is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We measured anti-pHERV-W, -syncytin-1 IgG and their Ratio (HERV-W) in 83 RR-MS patients and 112 healthy controls (HC). Age and sex-adjusted sNfL\/sGFAP Z-scores were derived from HC-calibrated GAMLSS models. HERV-W humoral responses were correlated with MS severity score (MSSS), cytokines (Olink\u2122), and clinical phases (acute MS [AMS], stable MS [SMS])\n                      <jats:italic>via<\/jats:italic>\n                      non-parametric tests and discriminant analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HERV-W showed no difference between MS patients and HC, consistent with stable low-EDSS RR-MS predominance. HERV-W ratio correlated positively with Z-sNfL (\u03c1=0.67, p=0.012), Z-sGFAP (\u03c1=0.54, p=0.048), MSSS, and proinflammatory cytokines (IL-6, IL-1\u03b2 and CXCL-9\/10) specifically in AMS and SMS-EDSS&amp;gt;4 subgroups. AMS patients with elevated sNfL (&amp;gt;10 pg\/ml; Z-score &amp;gt;1.5) exhibited markedly higher HERV-W than those with lower sNfl values. Discriminant models combining HERV-W, sNfL, and sGFAP achieved 82% of accuracy for MS-EDSS&amp;gt;4 classification; excluding HERV-W reduced the correct MS-EDSS&amp;gt;4 classification by 9.1%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HERV-W humoral activity shows state-specific associations with sNfL and sGFAP and proinflammatory status in acute and high-disability MS phases. These findings support integrating HERV-W humoral response into dynamic biomarker panels to better stratify patients by inflammatory burden and disability trajectory, positioning it as a cofactor linking immune dysregulation to neurodegeneration rather than a singular MS marker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1776117","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T05:21:27Z","timestamp":1774243287000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["HERV-W association with serum biomarkers NfL and GFAP in multiple sclerosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Stefano","family":"Ruberto","sequence":"first","affiliation":[{"name":"Grupo de Investigaci\u00f3n de Factores Ambientales en Enfermedades Degenerativas, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Red de Enfermedades Inflamatorias (REI), Red Espa\u00f1ola de Esclerosis M\u00faltiple","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria I.","family":"Dominguez-Mozo","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n de Factores Ambientales en Enfermedades Degenerativas, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Red de Enfermedades Inflamatorias (REI), Red Espa\u00f1ola de Esclerosis M\u00faltiple","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa Mar\u00eda","family":"Villar","sequence":"additional","affiliation":[{"name":"Servicio de Inmunolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, Red de Enfermedades Inflamatorias (REI), ISCIII, Red Espa\u00f1ola de Esclerosis M\u00faltiple, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucienne","family":"Costa-Frossard","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, Red de Enfermedades Inflamatorias (REI), Red Espa\u00f1ola de Esclerosis M\u00faltiple","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelia","family":"Villarrubia","sequence":"additional","affiliation":[{"name":"Servicio de Inmunolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, Red de Enfermedades Inflamatorias (REI), ISCIII, Red Espa\u00f1ola de Esclerosis M\u00faltiple, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yolanda","family":"Aladro","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, Hospital Universitario de Getafe","place":["Getafe, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"Casanova-Pe\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Torrej\u00f3n","place":["Torrej\u00f3n de Ardoz, Getafe, Spain"]},{"name":"School of Medicine, Francisco de Vitoria University","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00e9s","family":"Gonz\u00e1lez-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Unidad de Enfermedades Desmielinizantes, Hospital \u00c1lvaro Cunqueiro, Red de Enfermedades Inflamatorias (REI)","place":["Vigo, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Angel","family":"Garcia-Martinez","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n de Factores Ambientales en Enfermedades Degenerativas, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Red de Enfermedades Inflamatorias (REI), Red Espa\u00f1ola de Esclerosis M\u00faltiple","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Arroyo","sequence":"additional","affiliation":[{"name":"Departamento de Neurolog\u00eda, Hospital Universitario Quironsalud Madrid","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Alvarez-Lafuente","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n de Factores Ambientales en Enfermedades Degenerativas, Instituto de Investigaci\u00f3n Sanitaria del Hospital Cl\u00ednico San Carlos (IdISSC), Red de Enfermedades Inflamatorias (REI), Red Espa\u00f1ola de Esclerosis M\u00faltiple","place":["Madrid, 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