{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T09:13:52Z","timestamp":1768554832461,"version":"3.49.0"},"posted":{"date-parts":[[2022,4,25]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":58,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,5,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Infections by the Epstein-Barr virus (EBV) are often at the disease onset of patients suffering from Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS). However, serological analyses of these infections remain inconclusive when comparing patients with healthy controls. In particular, it is unclear if certain EBV-derived antigens eliciting antibody responses have a biomarker potential for disease diagnosis. With this purpose, we re-analysed a previously published microarray data on the IgG antibody responses against 3,054 EBV-related antigens in 92 patients with ME\/CFS and 50 HCs. This re-analysis consisted of constructing different regression models for binary outcomes with the ability to classify patients and HCs. In these models, we tested for a possible interaction of different antibodies with age and gender. When analyzing the whole data set, there were no antibody responses that could be used to distinguish patients from healthy controls. A similar finding was obtained when comparing patients with noninfectious or unknown disease trigger to healthy controls. However, when data analysis was restricted to the comparison between HCs and patients with a putative infection at disease onset, we could identify stronger antibody responses against two candidate antigens (EBNA4_0529 and EBNA6_0070). Using antibody responses to these two antigens together with age and gender, the final classification model had an estimated sensitivity and specificity of 0.833 and 0.720, respectively. This reliable case-control discrimination suggested the use of the antibody levels related to these candidate viral epitopes as biomarkers for disease diagnosis in this subgroup of patients. When a bioinformatic analysis was performed on these epitopes, it revealed a potential molecular mimicry with several human proteins. To confirm these promising findings, a follow-up study will be conducted in a separate cohort of patients.<\/jats:p>","DOI":"10.1101\/2022.04.20.22273990","type":"posted-content","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T12:45:25Z","timestamp":1653309925000},"source":"Crossref","is-referenced-by-count":1,"title":["Revisiting IgG antibody reactivity to Epstein-Barr virus in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome and its potential application to disease diagnosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8542-1706","authenticated-orcid":false,"given":"Nuno","family":"Sep\u00falveda","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-1483","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Malato","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1593-8563","authenticated-orcid":false,"given":"Franziska","family":"Sotzny","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1633-6345","authenticated-orcid":false,"given":"Anna D","family":"Grabowska","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8249-0354","authenticated-orcid":false,"given":"Andr\u00e9","family":"Fonseca","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1026-6078","authenticated-orcid":false,"given":"Clara","family":"Cordeiro","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-8500","authenticated-orcid":false,"given":"Lu\u00eds","family":"Gra\u00e7a","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8423-1823","authenticated-orcid":false,"given":"Przemyslaw","family":"Biecek","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8693-4386","authenticated-orcid":false,"given":"Uta","family":"Behrends","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8680-1065","authenticated-orcid":false,"given":"Josef","family":"Mautner","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4476-4198","authenticated-orcid":false,"given":"Francisco","family":"Westermeier","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5077-7868","authenticated-orcid":false,"given":"Eliana M","family":"Lacerda","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8554-9638","authenticated-orcid":false,"given":"Carmen","family":"Scheibenbogen","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2022052309065284000_2022.04.20.22273990v2.1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.587380"},{"key":"2022052309065284000_2022.04.20.22273990v2.2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2016.0271"},{"key":"2022052309065284000_2022.04.20.22273990v2.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj8222"},{"key":"2022052309065284000_2022.04.20.22273990v2.4","first-page":"590","article-title":"Chronic fatigue syndrome. 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