{"doi":"10.1101/2022.04.20.22273990","title":"Revisiting IgG antibody reactivity to Epstein-Barr virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and its potential application to disease diagnosis","abstract":"Abstract 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.","journal":"medRxiv","year":2022,"id":298254,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":773746,"name":"João Malato","orcid":"0000-0003-4389-1483","position":1,"is_corresponding":false},{"id":773747,"name":"Franziska Sotzny","orcid":"0000-0003-1593-8563","position":2,"is_corresponding":false},{"id":773751,"name":"Anna D. Grabowska","orcid":"0000-0003-1633-6345","position":3,"is_corresponding":false},{"id":773750,"name":"André Fonseca","orcid":"0000-0001-8249-0354","position":4,"is_corresponding":false},{"id":773752,"name":"Clara Cordeiro","orcid":"0000-0002-1026-6078","position":5,"is_corresponding":false},{"id":745648,"name":"Luís Graça","orcid":"0000-0001-6935-8500","position":6,"is_corresponding":false},{"id":859131,"name":"Przemysław Biecek","orcid":"0000-0001-8423-1823","position":7,"is_corresponding":false},{"id":74450,"name":"Uta Behrends","orcid":"0000-0002-8693-4386","position":8,"is_corresponding":false},{"id":987246,"name":"Josef Mautner","orcid":"0000-0002-8680-1065","position":9,"is_corresponding":false},{"id":773754,"name":"Francisco Westermeier","orcid":"0000-0002-4476-4198","position":10,"is_corresponding":false},{"id":277026,"name":"Eliana Lacerda","orcid":"0000-0002-5077-7868","position":11,"is_corresponding":false},{"id":773753,"name":"Carmen Scheibenbogen","orcid":"0000-0002-8554-9638","position":12,"is_corresponding":false},{"id":240624,"name":"Nuno Sepúlveda","orcid":"0000-0002-8542-1706","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:36.269611Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}