{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T18:39:05Z","timestamp":1764787145196,"version":"3.46.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Griffith University Disability and Rehabilitation Program"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gulf War Illness (GWI) is a chronic multisystemic illness found in one-third of Gulf War Veterans. The aetiology of GWI is elusive; however, is strongly associated with exposure to multiple toxic agents, environmental exposures, and prophylactic medications or vaccinations. In the literature, disruption of the immune system and the presence of inflammation have been reported in GWI. In this novel study, we report gene expression-based analysis of a panel of 785 immune function related gene markers in GWI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Ribonucleic acid (RNA) was extracted from peripheral blood mononuclear cells (PBMCs) isolated from n\u2009=\u200920 Australian GWI (CDC Case Definition and Kansas Criteria, 54.4\u2009\u00b1\u20090.74 years), and n\u2009=\u200915 healthy control (HC, 47.47\u2009\u00b1\u20092.91 years) participants. All participants were sex-matched (100% male). RNA gene expression was quantified using the NanoString\n                      <jats:sup>\u00ae<\/jats:sup>\n                      nCounter Immune Exhaustion panel and analysed using Rosalind Bio and IPA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty-three differentially expressed genes were identified, of which 21 were upregulated and 12 were downregulated in the GWI cohort. Upregulated genes included\n                      <jats:italic>SIGLEC1, BPI, MMP9, RSAD2, IFIT1\/2, CEACAM1\/3<\/jats:italic>\n                      and were associated with metabolic and cellular stress responses, while downregulated genes were associated with T cell receptor regions and humoral immune responses. Downregulated genes included\n                      <jats:italic>TRDV3, IGHG1, TRGV4, TRDV1\/4,<\/jats:italic>\n                      and\n                      <jats:italic>IL7<\/jats:italic>\n                      . Gene set analysis revealed associations between gene expression and type I interferon signalling, natural killer receptors, T cell receptors, and tumour necrosis factor signalling. Pathway analysis revealed the role of differentially expressed genes in neutrophil signalling and degranulation, toll-like receptor cascades, and the role of lipids\/lipid rafts in infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This investigation elucidates the potential role of immune dysregulation underlying GWI, emphasising the importance of immune exhaustion pathways in disease progression. Further investigations in a larger cohort may further elucidate or confirm these identified markers for potential screening or therapeutic applications in GWI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0338198","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T18:36:54Z","timestamp":1764787014000},"page":"e0338198","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune transcriptomic changes in Australian Gulf War veterans"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0815-3162","authenticated-orcid":true,"given":"Natalie","family":"Eaton-Fitch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etianne Martini","family":"Sasso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonya","family":"Marshall-Gradisnik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"issue":"1","key":"pone.0338198.ref001","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1093\/aje\/kwj008","article-title":"Chronic multisymptom illness complex in Gulf War I veterans 10 years later","volume":"163","author":"MS Blanchard","year":"2006","journal-title":"Am J Epidemiol"},{"key":"pone.0338198.ref002","unstructured":"Binns J, Bloom F, Bunker J, Crawford F, Golomb B, Klimas N, et al. 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