{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:18:55Z","timestamp":1788185935465,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"crossref","award":["IP-2020-02-8961"],"award-info":[{"award-number":["IP-2020-02-8961"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"crossref"}]},{"award":["IP-2020-02-8961"],"award-info":[{"award-number":["IP-2020-02-8961"]}],"id":[{"id":"https:\/\/ror.org\/03n51vw80","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Epstein\u2013Barr virus (EBV)-associated infectious mononucleosis (IM) elicits a robust cellular immune response; however, systemic chemokine profiles in pediatric IM and their diagnostic relevance remain insufficiently characterized. This study evaluated proinflammatory chemokine expression in children with acute EBV-associated IM and its relationship with disease presence and severity. Methods: In this retrospective study, 64 children with confirmed acute EBV-associated IM and 16 healthy controls were included. Clinical severity was classified using the Severity of Mononucleosis (SOM) scale. Plasma concentrations of 12 chemokines were quantified by bead-based flow cytometry. Groups were compared using nonparametric tests, and logistic regression with cross-validation identified predictors distinguishing IM from controls. Results: CXCL9, CXCL10, and CXCL11 concentrations were significantly elevated in IM patients compared with controls across all severity strata (p \u2264 0.011), with no differences between SOM categories. CXCL5 concentrations were lower in severe (SOM \u2265 2) than moderate disease (p = 0.037). Other chemokines showed no significant differences. CXCL9 and CXCL10 effectively distinguished IM (AUC = 0.86, sensitivity = 0.71, specificity = 0.96). Conclusions: IFN-\u03b3\u2013inducible chemokines CXCL9\u201311 are markedly elevated in pediatric EBV-associated IM, irrespective of clinical severity, whereas CXCL5 may be associated with disease severity. Prospective validation of these preliminary findings is strongly warranted.<\/jats:p>","DOI":"10.3390\/pathogens15050487","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T09:33:17Z","timestamp":1777627997000},"page":"487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Increased Expression of CXCL9, CXCL10, and CXCL11 in Epstein\u2013Barr Virus-Associated Infectious Mononucleosis and the Role of CXCL5 as a Candidate Biomarker of Disease Severity"],"prefix":"10.3390","volume":"15","author":[{"given":"Andrea","family":"Nik\u010devi\u0107","sequence":"first","affiliation":[{"name":"Department for Pediatric Infectious Diseases, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9362-7213","authenticated-orcid":false,"given":"Leona","family":"Radmani\u0107 Matotek","sequence":"additional","affiliation":[{"name":"Department of Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silva","family":"\u0160iftar","sequence":"additional","affiliation":[{"name":"Department for Pediatric Infectious Diseases, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna","family":"Stemberger Mari\u0107","sequence":"additional","affiliation":[{"name":"Department for Pediatric Infectious Diseases, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5153-5027","authenticated-orcid":false,"given":"Goran","family":"Te\u0161ovi\u0107","sequence":"additional","affiliation":[{"name":"Department for Pediatric Infectious Diseases, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia"},{"name":"Department of Infectious Diseases, University of Zagreb School of Medicine, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snjezana","family":"Zidovec-Lepej","sequence":"additional","affiliation":[{"name":"Department of Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"ref_1","unstructured":"International Committee for the Taxonomy of Viruses (2025, October 09). Genus: Lymphocryptovirus. Available online: https:\/\/ictv.global\/report\/chapter\/orthoherpesviridae\/orthoherpesviridae\/lymphocryptovirus."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.virusres.2009.07.005","article-title":"The extent of genetic diversity of Epstein-Barr virus and its geographic and disease patterns: A need for reappraisal","volume":"143","author":"Chang","year":"2009","journal-title":"Virus Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/rmv.1816","article-title":"Host genetics of Epstein-Barr virus infection, latency and disease","volume":"25","author":"Houldcroft","year":"2015","journal-title":"Rev. Med. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1086\/428097","article-title":"Long-term shedding of infectious Epstein-Barr virus after infectious mononucleosis","volume":"191","author":"Morand","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1182\/blood-2007-06-093278","article-title":"On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis","volume":"111","author":"Hadinoto","year":"2008","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3802","DOI":"10.4049\/jimmunol.139.11.3802","article-title":"Activated lymphocytes during acute Epstein-Barr virus infection","volume":"139","author":"Tomkinson","year":"1987","journal-title":"J. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Prtori\u0107, L., \u0160okota, A., Karabati\u0107 Knezovi\u0107, S., Te\u0161ovi\u0107, G., and Zidovec-Lepej, S. (2025). Clinical features and laboratory findings of hospitalized children with infectious mononucleosis caused by Epstein-Barr virus from Croatia. Pathogens, 14.","DOI":"10.3390\/pathogens14040374"},{"key":"ref_8","unstructured":"Mandell, G.L., Bennett, J.E., and Dolin, R. (2019). Epstein\u2013Barr virus (infectious mononucleosis, Epstein\u2013Barr virus-associated malignant diseases, and other diseases). Mandell, Douglas, and Bennett\u2019s Principles and Practice of Infectious Diseases, Elsevier. [9th ed.]."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1182\/blood.V57.5.933.933","article-title":"Clinical and laboratory evaluation of infants and children with Epstein-Barr virus-induced infectious mononucleosis: Report of 32 patients (aged 10\u201348 months)","volume":"57","author":"Horwitz","year":"1981","journal-title":"Blood"},{"key":"ref_10","first-page":"278","article-title":"Peritonsillar abscess and infectious mononucleosis: An association or a different presentation of the same condition?","volume":"92","author":"Monem","year":"1999","journal-title":"Ir. Med. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/S0025-6196(12)60835-0","article-title":"Spontaneous rupture of the spleen in patients with infectious mononucleosis","volume":"67","author":"Aldrete","year":"1992","journal-title":"Mayo Clin. Proc."},{"key":"ref_12","unstructured":"Fauci, A.S., Kasper, D.L., Longo, D.L., Hauser, S.L., Jameson, J.L., and Loscalzo, J. (2010). Epstein\u2013Barr virus infections, including infectious mononucleosis. Harrison\u2019s Principles of Internal Medicine, McGraw-Hill. [17th ed.]."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/path.4431","article-title":"Epstein-Barr virus-encoded EBNA1 and ZEBRA: Targets for therapeutic strategies against EBV-carrying cancers","volume":"235","author":"Daskalogianni","year":"2015","journal-title":"J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107fs7","DOI":"10.1126\/scitranslmed.3002878","article-title":"Epstein-Barr virus: An important vaccine target for cancer prevention","volume":"3","author":"Cohen","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1136\/adc.74.1.27","article-title":"The role of Epstein-Barr virus in Hodgkin\u2019s disease from different geographical areas","volume":"74","author":"Weinreb","year":"1996","journal-title":"Arch. Dis. Child."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13052-020-00949-7","article-title":"Clinical warning of hemophagocytic syndrome caused by Epstein-Barr virus","volume":"47","author":"Shi","year":"2021","journal-title":"Ital. J. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1097\/00000478-199511000-00011","article-title":"Lymphomatoid granulomatosis: Evidence of immunophenotypic diversity and relationship to Epstein-Barr virus infection","volume":"19","author":"Myers","year":"1995","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1146\/annurev.med.46.1.381","article-title":"Classification of Epstein-Barr virus-associated posttransplant lymphoproliferative diseases: Implications for understanding their pathogenesis and developing rational treatment strategies","volume":"46","author":"Hanto","year":"1995","journal-title":"Annu. Rev. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1126\/science.abj8222","article-title":"Longitudinal analysis reveals a high prevalence of Epstein-Barr virus associated with multiple sclerosis","volume":"375","author":"Bjornevik","year":"2022","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Loebel, M., Eckey, M., Sotzny, F., Hahn, E., Bauer, S., Grabowski, P., Zerweck, J., Holenya, P., Hanitsch, L.G., and Wittke, K. (2017). Serological profiling of the EBV immune response in chronic fatigue syndrome using a peptide microarray. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179124"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jason, L.A., and Katz, B.Z. (2025). Predisposing and precipitating factors in Epstein\u2013Barr virus-caused myalgic encephalomyelitis\/chronic fatigue syndrome. Microorganisms, 13.","DOI":"10.3390\/microorganisms13040702"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1111\/febs.14466","article-title":"A guide to chemokines and their receptors","volume":"285","author":"Hughes","year":"2018","journal-title":"FEBS J."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sheridan, G.K., Wdowicz, A., Pickering, M., Watters, O., Halley, P., O\u2019Sullivan, N.C., Mooney, C., O\u2019Connell, D.J., O\u2019Connor, J.J., and Murphy, K.J. (2014). CX3CL1 is up-regulated in the rat hippocampus during memory-associated synaptic plasticity. Front. Cell. Neurosci., 8.","DOI":"10.3389\/fncel.2014.00233"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.micinf.2011.10.003","article-title":"XCL1 and XCR1 in the immune system","volume":"14","author":"Lei","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1128\/JVI.78.4.1665-1674.2004","article-title":"Selective induction of Th2-attracting chemokines CCL17 and CCL22 in human B cells by latent membrane protein 1 of Epstein-Barr virus","volume":"78","author":"Nakayama","year":"2004","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9041","DOI":"10.1128\/JVI.00541-13","article-title":"Autocrine CCL3 and CCL4 induced by the oncoprotein LMP1 promote Epstein-Barr virus-triggered B cell proliferation","volume":"87","author":"Tsai","year":"2013","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Jorapur, A., Marshall, L.A., Jacobson, S., Xu, M., Marubayashi, S., Zibinsky, M., Hu, D.X., Robles, O., Jackson, J.J., and Baloche, V. (2022). EBV+ tumors exploit tumor cell-intrinsic and -extrinsic mechanisms to produce regulatory T cell-recruiting chemokines CCL17 and CCL22. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010200"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1365-2567.2005.02311.x","article-title":"Epstein-Barr virus infection negatively impacts the CXCR4-dependent migration of tonsillar B cells","volume":"117","author":"Mowafi","year":"2006","journal-title":"Immunology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jpeds.2019.01.035","article-title":"A validated scale for assessing the severity of acute infectious mononucleosis","volume":"209","author":"Katz","year":"2019","journal-title":"J. Pediatr."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Fevang, B., Wyller, V.B.B., Mollnes, T.E., Pedersen, M., Asprusten, T.T., Michelsen, A., Ueland, T., and Otterdal, K. (2021). Lasting immunological imprint of primary Epstein-Barr virus infection with associations to chronic low-grade inflammation and fatigue. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.715102"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4581","DOI":"10.1038\/s41467-025-59813-z","article-title":"Epstein-Barr virus induces aberrant B cell migration and diapedesis via FAK-dependent chemotaxis pathways","volume":"16","author":"Delecluse","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1111\/bjh.70095","article-title":"Interferon-gamma and C-X-C motif chemokine ligand 9: Which is better for haemophagocytic lymphohistiocytosis diagnosis and monitoring?","volume":"207","author":"Luo","year":"2025","journal-title":"Br. J. Haematol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/5\/487\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T04:14:40Z","timestamp":1777781680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/5\/487"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["pathogens15050487"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15050487","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]}}}