{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T10:21:12Z","timestamp":1793701272584,"version":"4.5.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"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>Introduction<\/jats:title>\n                    <jats:p>Colonoscopy remains the gold standard for diagnosing inflammatory bowel disease (IBD) even though it is an invasive and costly procedure. To enable non-invasive diagnosis, we aimed to identify blood-based transcriptomic biomarkers that specifically distinguish IBD from healthy and inflammatory controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Public microarray and RNA-seq datasets from whole blood of IBD, rheumatoid arthritis (RA), and control subjects were analyzed. RA was included as a positive control for systemic inflammation to filter out non-IBD-specific gene signatures. Differentially expressed genes (DEGs) were identified, followed by immune cell deconvolution (CIBERSORTx), pathway and network analysis, and diagnostic model construction using LASSO and SVM. A real-life cohort (36 IBD patients, 30 controls) was recruited for qRT-PCR validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IBD blood transcriptomes exhibited altered immune profiles, including increased M0 macrophages, Tregs, and CD4 na\u00efve T cells, and decreased memory B and activated NK cells. After excluding RA-overlapping DEGs, 25 IBD-specific DEGs with |log2FC| &amp;gt; 0.5 were prioritized. LASSO and SVM identified a three-mRNA panel\u2014IL4R, EIF5A, and SLC9A8\u2014which achieved 84% diagnostic accuracy in the discovery cohort and 99% accuracy in the real-life cohort. Network analysis highlighted NDUFB2 as a key downregulated hub gene linked to mitochondrial complex I dysfunction and oxidative phosphorylation disruption. Elevated oxidative stress in IBD was confirmed by increased Total Oxidant Status (TOS) levels in patient plasma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings support the use of peripheral blood transcriptomics for IBD diagnosis and demonstrate that a focused three-gene panel can achieve high diagnostic accuracy. The inclusion of RA as an inflammatory control enabled the identification of IBD-specific markers, minimizing confounding from general immune activation. These results provide a practical foundation for developing non-invasive diagnostic tools for clinical use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1570374","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T01:22:48Z","timestamp":1750382568000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Biomarker discovery for non-invasive diagnosis of inflammatory bowel disease using blood transcriptomics"],"prefix":"10.3389","volume":"16","author":[{"given":"Mohammad Hossein 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