{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T04:04:47Z","timestamp":1793851487633,"version":"4.6.1"},"reference-count":74,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T00:00:00Z","timestamp":1713484800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T00:00:00Z","timestamp":1713484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Immune thrombocytopenia (ITP), an acquired autoimmune disease, is characterized by immune-mediated platelet destruction. A biomarker is a biological entity that contributes to disease pathogenesis and reflects disease activity. Metabolic alterations are reported to be associated with the occurrence of various diseases. As metabolic biomarkers for ITP have not been identified. This study aimed to identify metabolism-related differentially expressed genes as potential biomarkers for pathogenesis of ITP using bioinformatic analyses.The microarray expression data of the peripheral blood mononuclear cells were downloaded from the Gene Expression Omnibus database (GSE112278 download link: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE112278\" ext-link-type=\"uri\">https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE112278<\/jats:ext-link>). Key module genes were intersected with metabolism-related genes to obtain the metabolism-related key candidate genes. The hub genes were screened based on the degree function in the coytoscape sofware. The key ITP-related genes were subjected to functional enrichment analysis. Immune infiltration analysis was performed using a single-sample gene set enrichment analysis algorithm to evaluate the differential infiltration levels of immune cell types between ITP patient and control. Molecular subtypes were identified based on the expression of hub genes. The expression of hub genes in the ITP patients was validated using quantitative real-time polymerase chain reaction analysis. This study identified five hub genes (<jats:italic>ADH4<\/jats:italic>, <jats:italic>CYP7A1<\/jats:italic>, <jats:italic>CYP1A2<\/jats:italic>, <jats:italic>CYP8B1<\/jats:italic>, and <jats:italic>NR1H4<\/jats:italic>), which were be associated with the pathogenesis of ITP, and two molecular subtypes of ITP. Among these hub genes, CYP7A1 and CYP8B1 involved in cholesterol metabolism,were further verified in clinical samples.<\/jats:p>","DOI":"10.1038\/s41598-024-59493-7","type":"journal-article","created":{"date-parts":[[2024,4,21]],"date-time":"2024-04-21T18:09:10Z","timestamp":1713722950000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of metabolism-related key genes as potential biomarkers for pathogenesis of immune thrombocytopenia"],"prefix":"10.1038","volume":"14","author":[{"given":"Xiangmei","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyun","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengqiang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jirui","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,19]]},"reference":[{"key":"59493_CR1","doi-asserted-by":"publisher","first-page":"2386","DOI":"10.1182\/blood-2008-07-162503","volume":"113","author":"F Rodeghiero","year":"2009","unstructured":"Rodeghiero, F. et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: Report from an international working group. Blood 113, 2386\u20132393. https:\/\/doi.org\/10.1182\/blood-2008-07-162503 (2009).","journal-title":"Blood"},{"key":"59493_CR2","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.revmed.2016.12.016","volume":"38","author":"G Moulis","year":"2017","unstructured":"Moulis, G., Lapeyre-Mestre, M., Adoue, D. & Sailler, L. Epidemiology and pharmacoepidemiology of immune thrombocytopenia. La Revue de medecine interne 38, 444\u2013449. https:\/\/doi.org\/10.1016\/j.revmed.2016.12.016 (2017).","journal-title":"La Revue de medecine interne"},{"key":"59493_CR3","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1111\/bjh.12869","volume":"166","author":"H Frederiksen","year":"2014","unstructured":"Frederiksen, H., Maegbaek, M. L. & N\u00f8rgaard, M. Twenty-year mortality of adult patients with primary immune thrombocytopenia: A Danish population-based cohort study. Br. J. Haematol. 166, 260\u2013267. https:\/\/doi.org\/10.1111\/bjh.12869 (2014).","journal-title":"Br. J. Haematol."},{"key":"59493_CR4","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.3892\/etm.2018.6508","volume":"16","author":"L Dai","year":"2018","unstructured":"Dai, L. et al. Altered circulating T follicular helper cells in patients with chronic immune thrombocytopenia. Exp. Ther. Med. 16, 2471\u20132477. https:\/\/doi.org\/10.3892\/etm.2018.6508 (2018).","journal-title":"Exp. Ther. Med."},{"key":"59493_CR5","doi-asserted-by":"publisher","first-page":"100097","DOI":"10.1016\/j.rpth.2023.100097","volume":"7","author":"S Mahamad","year":"2023","unstructured":"Mahamad, S. et al. Proceedings of the immune thrombocytopenia summit: New concepts in mechanisms, diagnosis, and management. Res. Pract. Thromb. Haemost. 7, 100097. https:\/\/doi.org\/10.1016\/j.rpth.2023.100097 (2023).","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"59493_CR6","doi-asserted-by":"publisher","DOI":"10.3390\/jcm6020016","author":"A Zufferey","year":"2017","unstructured":"Zufferey, A., Kapur, R. & Semple, J. W. Pathogenesis\u00a0and\u00a0therapeutic\u00a0mechanisms\u00a0in immune\u00a0thrombocytopenia\u00a0(ITP). J. Clin. Med. https:\/\/doi.org\/10.3390\/jcm6020016 (2017).","journal-title":"J. Clin. Med."},{"key":"59493_CR7","doi-asserted-by":"publisher","first-page":"2414","DOI":"10.1182\/bloodadvances.2017010942","volume":"1","author":"DM Arnold","year":"2017","unstructured":"Arnold, D. M. et al. Misdiagnosis of primary immune thrombocytopenia and frequency of bleeding: Lessons from the McMaster ITP Registry. Blood Adv. 1, 2414\u20132420. https:\/\/doi.org\/10.1182\/bloodadvances.2017010942 (2017).","journal-title":"Blood Adv."},{"key":"59493_CR8","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13045-023-01401-z","volume":"16","author":"XG Liu","year":"2023","unstructured":"Liu, X. G., Hou, Y. & Hou, M. How we treat primary immune thrombocytopenia in adults. J. Hematol. Oncol. 16, 4. https:\/\/doi.org\/10.1186\/s13045-023-01401-z (2023).","journal-title":"J. Hematol. Oncol."},{"key":"59493_CR9","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1002\/rth2.12388","volume":"4","author":"AZ Cheloff","year":"2020","unstructured":"Cheloff, A. Z., Kuter, D. J. & Al-Samkari, H. Serum complement levels in immune thrombocytopenia: Characterization and relation to clinical features. Res. Pract. Thromb. Haemost. 4, 807\u2013812. https:\/\/doi.org\/10.1002\/rth2.12388 (2020).","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"59493_CR10","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1002\/ajh.24702","volume":"92","author":"G Moulis","year":"2017","unstructured":"Moulis, G. et al. Newly diagnosed immune thrombocytopenia adults: Clinical epidemiology, exposure to treatments, and evolution. Results of the CARMEN multicenter prospective cohort. Am. J. Hematol. 92, 493\u2013500. https:\/\/doi.org\/10.1002\/ajh.24702 (2017).","journal-title":"Am. J. Hematol."},{"key":"59493_CR11","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1182\/bloodadvances.2019001215","volume":"4","author":"Y Migdady","year":"2020","unstructured":"Migdady, Y. et al. Successful treatment of thrombocytopenia with daratumumab after allogeneic transplant: A case report and literature review. Blood Adv. 4, 815\u2013818. https:\/\/doi.org\/10.1182\/bloodadvances.2019001215 (2020).","journal-title":"Blood Adv."},{"key":"59493_CR12","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1017\/s0029665116002974","volume":"76","author":"A O'Gorman","year":"2017","unstructured":"O\u2019Gorman, A. & Brennan, L. The role of metabolomics in determination of new dietary biomarkers. Proc. Nutr. Soc. 76, 295\u2013302. https:\/\/doi.org\/10.1017\/s0029665116002974 (2017).","journal-title":"Proc. Nutr. Soc."},{"key":"59493_CR13","doi-asserted-by":"publisher","first-page":"845275","DOI":"10.3389\/fphar.2022.845275","volume":"13","author":"Z Zhang","year":"2022","unstructured":"Zhang, Z. et al. Plasma metabolomics identifies the dysregulated metabolic profile of primary immune thrombocytopenia (ITP) based on GC-MS. Front. Pharmacol. 13, 845275. https:\/\/doi.org\/10.3389\/fphar.2022.845275 (2022).","journal-title":"Front. Pharmacol."},{"key":"59493_CR14","doi-asserted-by":"publisher","first-page":"e129","DOI":"10.3324\/haematol.2019.226688","volume":"105","author":"H Zhang","year":"2020","unstructured":"Zhang, H. et al. Blood transcriptome and clonal T-cell correlates of response and non-response to eltrombopag therapy in a cohort of patients with chronic immune thrombocytopenia. Haematologica 105, e129\u2013e132. https:\/\/doi.org\/10.3324\/haematol.2019.226688 (2020).","journal-title":"Haematologica"},{"key":"59493_CR15","doi-asserted-by":"publisher","first-page":"275","DOI":"10.22037\/ijpr.2020.113442.14305","volume":"19","author":"S Gilanchi","year":"2020","unstructured":"Gilanchi, S. et al. Identification of candidate biomarkers for idiopathic thrombocytopenic purpura by bioinformatics analysis of microarray data. Iran. J. Pharm. Res. IJPR 19, 275\u2013289. https:\/\/doi.org\/10.22037\/ijpr.2020.113442.14305 (2020).","journal-title":"Iran. J. Pharm. Res. IJPR"},{"key":"59493_CR16","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1186\/1752-0509-8-s4-s11","volume":"8","author":"CH Chin","year":"2014","unstructured":"Chin, C. H. et al. cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol. 8, S11. https:\/\/doi.org\/10.1186\/1752-0509-8-s4-s11 (2014).","journal-title":"BMC Syst. Biol."},{"key":"59493_CR17","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1186\/s12885-021-08351-0","volume":"21","author":"L Hong","year":"2021","unstructured":"Hong, L. et al. A stemness-based eleven-gene signature correlates with the clinical outcome of hepatocellular carcinoma. BMC Cancer 21, 716. https:\/\/doi.org\/10.1186\/s12885-021-08351-0 (2021).","journal-title":"BMC Cancer"},{"key":"59493_CR18","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s12958-023-01079-5","volume":"21","author":"Y Chen","year":"2023","unstructured":"Chen, Y. et al. Constructing a seventeen-gene signature model for non-obstructive azoospermia based on integrated transcriptome analyses and WGCNA. Reprod. Biol. Endocrinol. RB&E 21, 30. https:\/\/doi.org\/10.1186\/s12958-023-01079-5 (2023).","journal-title":"Reprod. Biol. Endocrinol. RB&E"},{"key":"59493_CR19","doi-asserted-by":"publisher","DOI":"10.3390\/biology11060904","author":"J Lu","year":"2022","unstructured":"Lu, J. et al. Analysis of physiological and transcriptomic differences between a premature senescence mutant (GSm) and its wild-type in common wheat (Triticum aestivum L.). Biology https:\/\/doi.org\/10.3390\/biology11060904 (2022).","journal-title":"Biology"},{"key":"59493_CR20","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U. S. A. 102, 15545\u201315550. https:\/\/doi.org\/10.1073\/pnas.0506580102 (2005).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"59493_CR21","doi-asserted-by":"publisher","first-page":"1085700","DOI":"10.3389\/fgene.2022.1085700","volume":"13","author":"L Zhu","year":"2022","unstructured":"Zhu, L. et al. Effects of immune inflammation in head and neck squamous cell carcinoma: Tumor microenvironment, drug resistance, and clinical outcomes. Front. Genet. 13, 1085700. https:\/\/doi.org\/10.3389\/fgene.2022.1085700 (2022).","journal-title":"Front. Genet."},{"key":"59493_CR22","doi-asserted-by":"publisher","first-page":"104410","DOI":"10.1016\/j.ebiom.2022.104410","volume":"87","author":"F Wu","year":"2023","unstructured":"Wu, F. et al. Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes. EBioMedicine 87, 104410. https:\/\/doi.org\/10.1016\/j.ebiom.2022.104410 (2023).","journal-title":"EBioMedicine"},{"key":"59493_CR23","doi-asserted-by":"publisher","first-page":"2159794","DOI":"10.1155\/2022\/2159794","volume":"2022","author":"X Qiao","year":"2022","unstructured":"Qiao, X. et al. Exploring the interplay between metabolism and tumor microenvironment based on four major metabolism pathways in colon adenocarcinoma. J. Oncol. 2022, 2159794. https:\/\/doi.org\/10.1155\/2022\/2159794 (2022).","journal-title":"J. Oncol."},{"key":"59493_CR24","doi-asserted-by":"publisher","first-page":"16540","DOI":"10.1002\/jcp.28324","volume":"234","author":"XY Peng","year":"2019","unstructured":"Peng, X. Y., Wang, Y., Hu, H., Zhang, X. J. & Li, Q. Identification of the molecular subgroups in coronary artery disease by gene expression profiles. J. Cell. Physiol. 234, 16540\u201316548. https:\/\/doi.org\/10.1002\/jcp.28324 (2019).","journal-title":"J. Cell. Physiol."},{"key":"59493_CR25","doi-asserted-by":"publisher","first-page":"945","DOI":"10.3892\/ijo.2016.3330","volume":"48","author":"T Okano","year":"2016","unstructured":"Okano, T. et al. Identification of haptoglobin peptide as a novel serum biomarker for lung squamous cell carcinoma by serum proteome and peptidome profiling. Int. J. Oncol. 48, 945\u2013952. https:\/\/doi.org\/10.3892\/ijo.2016.3330 (2016).","journal-title":"Int. J. Oncol."},{"key":"59493_CR26","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1080\/21645515.2017.1342913","volume":"14","author":"Y Wang","year":"2018","unstructured":"Wang, Y. et al. Percentages of PD-1(+)CD4(+)T cells and PD-L1(+)DCs are increased and sPD-1 level is elevated in patients with immune thrombocytopenia. Hum. Vaccines Immunother. 14, 832\u2013838. https:\/\/doi.org\/10.1080\/21645515.2017.1342913 (2018).","journal-title":"Hum. Vaccines Immunother."},{"key":"59493_CR27","doi-asserted-by":"publisher","first-page":"810612","DOI":"10.3389\/fmed.2022.810612","volume":"9","author":"X Yu","year":"2022","unstructured":"Yu, X. et al. Associations of gut microbiota and fatty metabolism with immune thrombocytopenia. Front. Med. (Lausanne) 9, 810612. https:\/\/doi.org\/10.3389\/fmed.2022.810612 (2022).","journal-title":"Front. Med. (Lausanne)"},{"key":"59493_CR28","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1097\/mib.0000000000000193","volume":"21","author":"L V\u00edtek","year":"2015","unstructured":"V\u00edtek, L. Bile acid malabsorption in inflammatory bowel disease. Inflamm. Bowel Dis. 21, 476\u2013483. https:\/\/doi.org\/10.1097\/mib.0000000000000193 (2015).","journal-title":"Inflamm. Bowel Dis."},{"key":"59493_CR29","doi-asserted-by":"publisher","first-page":"e005","DOI":"10.1621\/nrs.08005","volume":"8","author":"S Modica","year":"2010","unstructured":"Modica, S., Gadaleta, R. M. & Moschetta, A. Deciphering the nuclear bile acid receptor FXR paradigm. Nuclear Receptor Signal. 8, e005. https:\/\/doi.org\/10.1621\/nrs.08005 (2010).","journal-title":"Nuclear Receptor Signal."},{"key":"59493_CR30","doi-asserted-by":"publisher","first-page":"2527","DOI":"10.3892\/ol.2014.2522","volume":"8","author":"WH Liu","year":"2014","unstructured":"Liu, W. H. et al. B7\u2013H4 expression in bladder urothelial carcinoma and immune escape mechanisms. Oncol. Lett. 8, 2527\u20132534. https:\/\/doi.org\/10.3892\/ol.2014.2522 (2014).","journal-title":"Oncol. Lett."},{"key":"59493_CR31","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13075-021-02709-2","volume":"24","author":"C Orvain","year":"2022","unstructured":"Orvain, C. et al. Acazicolcept (ALPN-101), a dual ICOS\/CD28 antagonist, demonstrates efficacy in systemic sclerosis preclinical mouse models. Arthritis Res. Ther. 24, 13. https:\/\/doi.org\/10.1186\/s13075-021-02709-2 (2022).","journal-title":"Arthritis Res. Ther."},{"key":"59493_CR32","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1165\/rcmb.2013-0171OC","volume":"51","author":"T Nakajima","year":"2014","unstructured":"Nakajima, T. et al. T cells and lung injury. Impact of rapamycin. Am. J. Respir. Cell Mol. Biol. 51, 294\u2013299. https:\/\/doi.org\/10.1165\/rcmb.2013-0171OC (2014).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"59493_CR33","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/nature08155","volume":"460","author":"K Araki","year":"2009","unstructured":"Araki, K. et al. mTOR regulates memory CD8 T-cell differentiation. Nature 460, 108\u2013112. https:\/\/doi.org\/10.1038\/nature08155 (2009).","journal-title":"Nature"},{"key":"59493_CR34","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.coi.2010.08.010","volume":"22","author":"C Peter","year":"2010","unstructured":"Peter, C., Waldmann, H. & Cobbold, S. P. mTOR signalling and metabolic regulation of T cell differentiation. Curr. Opin. Immunol. 22, 655\u2013661. https:\/\/doi.org\/10.1016\/j.coi.2010.08.010 (2010).","journal-title":"Curr. Opin. Immunol."},{"key":"59493_CR35","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.immuni.2009.04.014","volume":"30","author":"GM Delgoffe","year":"2009","unstructured":"Delgoffe, G. M. et al. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 30, 832\u2013844. https:\/\/doi.org\/10.1016\/j.immuni.2009.04.014 (2009).","journal-title":"Immunity"},{"key":"59493_CR36","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/ni.2005","volume":"12","author":"GM Delgoffe","year":"2011","unstructured":"Delgoffe, G. M. et al. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat. Immunol. 12, 295\u2013303. https:\/\/doi.org\/10.1038\/ni.2005 (2011).","journal-title":"Nat. Immunol."},{"key":"59493_CR37","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.immuni.2010.06.002","volume":"32","author":"K Lee","year":"2010","unstructured":"Lee, K. et al. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 32, 743\u2013753. https:\/\/doi.org\/10.1016\/j.immuni.2010.06.002 (2010).","journal-title":"Immunity"},{"key":"59493_CR38","doi-asserted-by":"publisher","first-page":"2798","DOI":"10.7150\/ijbs.33779","volume":"15","author":"Q Wang","year":"2019","unstructured":"Wang, Q. et al. Disrupted balance of CD4(+) T-cell subsets in bone marrow of patients with primary immune thrombocytopenia. Int. J. Biol. Sci. 15, 2798\u20132814. https:\/\/doi.org\/10.7150\/ijbs.33779 (2019).","journal-title":"Int. J. Biol. Sci."},{"key":"59493_CR39","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3389\/fmed.2020.00110","volume":"7","author":"Y Feng","year":"2020","unstructured":"Feng, Y. et al. Sirolimus as rescue therapy for refractory\/relapsed immune thrombocytopenia: Results of a single-center, prospective, single-arm study. Front. Med. 7, 110. https:\/\/doi.org\/10.3389\/fmed.2020.00110 (2020).","journal-title":"Front. Med."},{"key":"59493_CR40","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1159\/000452300","volume":"94","author":"H Yang","year":"2016","unstructured":"Yang, H. & Duan, Z. Bile acids and the potential role in primary biliary cirrhosis. Digestion 94, 145\u2013153. https:\/\/doi.org\/10.1159\/000452300 (2016).","journal-title":"Digestion"},{"key":"59493_CR41","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1159\/000382019","volume":"7","author":"MM Berrien-Elliott","year":"2015","unstructured":"Berrien-Elliott, M. M., Wagner, J. A. & Fehniger, T. A. Human cytokine-induced memory-like natural killer cells. J. Innate Immun. 7, 563\u2013571. https:\/\/doi.org\/10.1159\/000382019 (2015).","journal-title":"J. Innate Immun."},{"key":"59493_CR42","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1084\/jem.180.3.1097","volume":"180","author":"O Lantz","year":"1994","unstructured":"Lantz, O. & Bendelac, A. An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans. J. Exp. Med. 180, 1097\u20131106. https:\/\/doi.org\/10.1084\/jem.180.3.1097 (1994).","journal-title":"J. Exp. Med."},{"key":"59493_CR43","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/nri1309","volume":"4","author":"DI Godfrey","year":"2004","unstructured":"Godfrey, D. I., MacDonald, H. R., Kronenberg, M., Smyth, M. J. & Van Kaer, L. NKT cells: What\u2019s in a name?. Nat. Rev. Immunol. 4, 231\u2013237. https:\/\/doi.org\/10.1038\/nri1309 (2004).","journal-title":"Nat. Rev. Immunol."},{"key":"59493_CR44","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1146\/annurev.immunol.15.1.535","volume":"15","author":"A Bendelac","year":"1997","unstructured":"Bendelac, A., Rivera, M. N., Park, S. H. & Roark, J. H. Mouse CD1-specific NK1 T cells: Development, specificity, and function. Annu. Rev. Immunol. 15, 535\u2013562. https:\/\/doi.org\/10.1146\/annurev.immunol.15.1.535 (1997).","journal-title":"Annu. Rev. Immunol."},{"key":"59493_CR45","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.hemonc.2017.01.001","volume":"10","author":"FH El-Rashedi","year":"2017","unstructured":"El-Rashedi, F. H., El-Hawy, M. A., Helwa, M. A. & Abd-Allah, S. S. Study of CD4(+), CD8(+), and natural killer cells (CD16(+), CD56(+)) in children with immune thrombocytopenic purpura. Hematol. Oncol. Stem Cell Ther. 10, 8\u201314. https:\/\/doi.org\/10.1016\/j.hemonc.2017.01.001 (2017).","journal-title":"Hematol. Oncol. Stem Cell Ther."},{"key":"59493_CR46","doi-asserted-by":"publisher","first-page":"2706","DOI":"10.1182\/blood-2008-05-159285","volume":"113","author":"DM Benson Jr","year":"2009","unstructured":"Benson, D. M. Jr. et al. Stem cell factor and interleukin-2\/15 combine to enhance MAPK-mediated proliferation of human natural killer cells. Blood 113, 2706\u20132714. https:\/\/doi.org\/10.1182\/blood-2008-05-159285 (2009).","journal-title":"Blood"},{"key":"59493_CR47","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.3892\/mmr.2019.9929","volume":"19","author":"Q Zhang","year":"2019","unstructured":"Zhang, Q. et al. Prediction and analysis of weighted genes in hepatocellular carcinoma using bioinformatics analysis. Mol. Med. Rep. 19, 2479\u20132488. https:\/\/doi.org\/10.3892\/mmr.2019.9929 (2019).","journal-title":"Mol. Med. Rep."},{"key":"59493_CR48","doi-asserted-by":"publisher","first-page":"41964","DOI":"10.1038\/srep41964","volume":"7","author":"X Jiang","year":"2017","unstructured":"Jiang, X. et al. Micheliolide provides protection of mice against Staphylococcus aureus and MRSA infection by down-regulating inflammatory response. Sci. Rep. 7, 41964. https:\/\/doi.org\/10.1038\/srep41964 (2017).","journal-title":"Sci. Rep."},{"key":"59493_CR49","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1186\/s12879-019-4564-4","volume":"19","author":"YK Yeh","year":"2019","unstructured":"Yeh, Y. K., Ding, J. Y., Ku, C. L. & Chen, W. C. Disseminated Mycobacterium avium complex infection mimicking malignancy in a patient with anti-IFN-\u03b3 autoantibodies: A case report. BMC Infect. Dis. 19, 909. https:\/\/doi.org\/10.1186\/s12879-019-4564-4 (2019).","journal-title":"BMC Infect. Dis."},{"key":"59493_CR50","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3345\/cep.2022.00920","volume":"66","author":"FM El-Gendy","year":"2023","unstructured":"El-Gendy, F. M., Shehata, A. M. F., El-Kawy, E. A. A. & El-Hawy, M. A. Changes and correlations of T-cell coinhibitory molecule programmed death-1 and interferon-\u03b3 in pediatric immune thrombocytopenia. Clin. Exp. Pediatr. 66, 127\u2013133. https:\/\/doi.org\/10.3345\/cep.2022.00920 (2023).","journal-title":"Clin. Exp. Pediatr."},{"key":"59493_CR51","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1002\/bmc.736","volume":"21","author":"E Begas","year":"2007","unstructured":"Begas, E., Kouvaras, E., Tsakalof, A., Papakosta, S. & Asprodini, E. K. In vivo evaluation of CYP1A2, CYP2A6, NAT-2 and xanthine oxidase activities in a Greek population sample by the RP-HPLC monitoring of caffeine metabolic ratios. Biomed. Chromatogr. BMC 21, 190\u2013200. https:\/\/doi.org\/10.1002\/bmc.736 (2007).","journal-title":"Biomed. Chromatogr. BMC"},{"key":"59493_CR52","doi-asserted-by":"publisher","first-page":"e37","DOI":"10.1002\/humu.23855","volume":"40","author":"MR Botton","year":"2019","unstructured":"Botton, M. R. et al. Structural variation at the CYP2C locus: Characterization of deletion and duplication alleles. Hum. Mutat. 40, e37\u2013e51. https:\/\/doi.org\/10.1002\/humu.23855 (2019).","journal-title":"Hum. Mutat."},{"key":"59493_CR53","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1007\/s00296-009-1050-0","volume":"30","author":"MC Cornelis","year":"2010","unstructured":"Cornelis, M. C., Bae, S. C., Kim, I. & El-Sohemy, A. CYP1A2 genotype and rheumatoid arthritis in Koreans. Rheumatol. Int. 30, 1349\u20131354. https:\/\/doi.org\/10.1007\/s00296-009-1050-0 (2010).","journal-title":"Rheumatol. Int."},{"key":"59493_CR54","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1249\/mss.0000000000001519","volume":"50","author":"C Wu","year":"2018","unstructured":"Wu, C. et al. Beneficial effects of exercise pretreatment in a sporadic Alzheimer\u2019s rat model. Med. Sci. Sports Exerc. 50, 945\u2013956. https:\/\/doi.org\/10.1249\/mss.0000000000001519 (2018).","journal-title":"Med. Sci. Sports Exerc."},{"key":"59493_CR55","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1159\/000517812","volume":"145","author":"D Xu","year":"2022","unstructured":"Xu, D. et al. Preliminary study on apoptotic proteins in platelet from adult patients with chronic immune thrombocytopenic purpura. Acta Haematol. 145, 318\u2013325. https:\/\/doi.org\/10.1159\/000517812 (2022).","journal-title":"Acta Haematol."},{"key":"59493_CR56","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1038\/nm.3882","volume":"21","author":"S Hong","year":"2015","unstructured":"Hong, S. et al. Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. Nat. Med. 21, 887\u2013894. https:\/\/doi.org\/10.1038\/nm.3882 (2015).","journal-title":"Nat. Med."},{"key":"59493_CR57","doi-asserted-by":"publisher","first-page":"2101480","DOI":"10.1155\/2020\/2101480","volume":"2020","author":"F Zhang","year":"2020","unstructured":"Zhang, F. et al. The effects of preoperative oral carbohydrate on frequency of T and NK cells in patients with cervical cancer treated using neoadjuvant chemotherapy and surgery: A prospective cohort study. Biomed. Res. Int. 2020, 2101480. https:\/\/doi.org\/10.1155\/2020\/2101480 (2020).","journal-title":"Biomed. Res. Int."},{"key":"59493_CR58","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1177\/15353702211009787","volume":"246","author":"Q Li","year":"2021","unstructured":"Li, Q. et al. Regulation of Th1\/Th2 and Th17\/Treg by pDC\/mDC imbalance in primary immune thrombocytopenia. Exp. Biol. Med. (Maywood, N.Y.) 246, 1688\u20131697. https:\/\/doi.org\/10.1177\/15353702211009787 (2021).","journal-title":"Exp. Biol. Med. (Maywood, N.Y.)"},{"key":"59493_CR59","doi-asserted-by":"publisher","first-page":"44486","DOI":"10.1038\/srep44486","volume":"7","author":"HJ Lee","year":"2017","unstructured":"Lee, H. J., Kim, S. N., Jeon, M. S., Yi, T. & Song, S. U. ICOSL expression in human bone marrow-derived mesenchymal stem cells promotes induction of regulatory T cells. Sci. Rep. 7, 44486. https:\/\/doi.org\/10.1038\/srep44486 (2017).","journal-title":"Sci. Rep."},{"key":"59493_CR60","doi-asserted-by":"publisher","first-page":"110943","DOI":"10.1016\/j.celrep.2022.110943","volume":"39","author":"H Xiang","year":"2022","unstructured":"Xiang, H. et al. Vps33B controls Treg cell suppressive function through inhibiting lysosomal nutrient sensing complex-mediated mTORC1 activation. Cell Rep. 39, 110943. https:\/\/doi.org\/10.1016\/j.celrep.2022.110943 (2022).","journal-title":"Cell Rep."},{"key":"59493_CR61","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14184398","author":"CR Lai","year":"2022","unstructured":"Lai, C. R. et al. Farnesoid X receptor overexpression decreases the migration, invasion and angiogenesis of human bladder cancers via AMPK activation and cholesterol biosynthesis inhibition. Cancers https:\/\/doi.org\/10.3390\/cancers14184398 (2022).","journal-title":"Cancers"},{"key":"59493_CR62","doi-asserted-by":"publisher","first-page":"12216","DOI":"10.1016\/S0021-9258(18)98884-8","volume":"266","author":"R Chakrabarti","year":"1991","unstructured":"Chakrabarti, R. & Engleman, E. G. Interrelationships between mevalonate metabolism and the mitogenic signaling pathway in T lymphocyte proliferation. J. Biol. Chem. 266, 12216\u201312222 (1991).","journal-title":"J. Biol. Chem."},{"key":"59493_CR63","doi-asserted-by":"publisher","first-page":"337","DOI":"10.2147\/jbm.S358993","volume":"13","author":"R Hamzah","year":"2022","unstructured":"Hamzah, R. et al. Clinical epidemiology, treatment outcome and mortality rate of newly diagnosed immune thrombocytopenia in adult multicentre study in Malaysia. J. Blood Med. 13, 337\u2013349. https:\/\/doi.org\/10.2147\/jbm.S358993 (2022).","journal-title":"J. Blood Med."},{"key":"59493_CR64","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1111\/bjh.17938","volume":"201","author":"P Xu","year":"2023","unstructured":"Xu, P. et al. Atorvastatin restores imbalance of cluster of differentiation 4 (CD4)(+) T cells in immune thrombocytopenia in vivo and in vitro. Br. J. Haematol. 201, 530\u2013541. https:\/\/doi.org\/10.1111\/bjh.17938 (2023).","journal-title":"Br. J. Haematol."},{"key":"59493_CR65","doi-asserted-by":"publisher","first-page":"204","DOI":"10.3389\/fendo.2019.00204","volume":"10","author":"H Oguro","year":"2019","unstructured":"Oguro, H. The roles of cholesterol and its metabolites in normal and malignant hematopoiesis. Front. Endocrinol. 10, 204. https:\/\/doi.org\/10.3389\/fendo.2019.00204 (2019).","journal-title":"Front. Endocrinol."},{"key":"59493_CR66","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/s41435-021-00139-3","volume":"22","author":"S Chakraborty","year":"2021","unstructured":"Chakraborty, S., Pramanik, J. & Mahata, B. Revisiting steroidogenesis and its role in immune regulation with the advanced tools and technologies. Genes Immunity 22, 125\u2013140. https:\/\/doi.org\/10.1038\/s41435-021-00139-3 (2021).","journal-title":"Genes Immunity"},{"key":"59493_CR67","first-page":"17","volume":"54","author":"WH Holms","year":"1987","unstructured":"Holms, W. H. Control of flux through the citric acid cycle and the glyoxylate bypass in Escherichia coli. Biochem. Soc. Sympos. 54, 17\u201331 (1987).","journal-title":"Biochem. Soc. Sympos."},{"key":"59493_CR68","doi-asserted-by":"publisher","DOI":"10.3390\/life11010069","author":"I Choi","year":"2021","unstructured":"Choi, I., Son, H. & Baek, J. H. Tricarboxylic acid (TCA) cycle intermediates: Regulators of immune responses. Life (Basel, Switzerland) https:\/\/doi.org\/10.3390\/life11010069 (2021).","journal-title":"Life (Basel, Switzerland)"},{"key":"59493_CR69","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.cmet.2016.06.004","volume":"24","author":"V Lampropoulou","year":"2016","unstructured":"Lampropoulou, V. et al. Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation. Cell Metab. 24, 158\u2013166. https:\/\/doi.org\/10.1016\/j.cmet.2016.06.004 (2016).","journal-title":"Cell Metab."},{"key":"59493_CR70","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1089\/scd.2023.0154","volume":"32","author":"Z Liang","year":"2023","unstructured":"Liang, Z. et al. Mesenchymal stromal cells regulate M1\/M2 macrophage polarization in mice with immune thrombocytopenia. Stem Cells Dev. 32, 703\u2013714. https:\/\/doi.org\/10.1089\/scd.2023.0154 (2023).","journal-title":"Stem Cells Dev."},{"key":"59493_CR71","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1111\/jth.13767","volume":"15","author":"Q Feng","year":"2017","unstructured":"Feng, Q. et al. High-dose dexamethasone or all-trans-retinoic acid restores the balance of macrophages towards M2 in immune thrombocytopenia. J. Thromb. Haemost. JTH 15, 1845\u20131858. https:\/\/doi.org\/10.1111\/jth.13767 (2017).","journal-title":"J. Thromb. Haemost. JTH"},{"key":"59493_CR72","doi-asserted-by":"publisher","first-page":"e0153355","DOI":"10.1371\/journal.pone.0153355","volume":"11","author":"JM Yabu","year":"2016","unstructured":"Yabu, J. M., Siebert, J. C. & Maecker, H. T. Immune profiles to predict response to desensitization therapy in highly HLA-sensitized kidney transplant candidates. PloS One 11, e0153355. https:\/\/doi.org\/10.1371\/journal.pone.0153355 (2016).","journal-title":"PloS One"},{"key":"59493_CR73","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/imr.12634","volume":"282","author":"K Mukai","year":"2018","unstructured":"Mukai, K., Tsai, M., Saito, H. & Galli, S. J. Mast cells as sources of cytokines, chemokines, and growth factors. Immunol. Rev. 282, 121\u2013150. https:\/\/doi.org\/10.1111\/imr.12634 (2018).","journal-title":"Immunol. Rev."},{"key":"59493_CR74","first-page":"2419","volume":"11","author":"N Okamoto","year":"2018","unstructured":"Okamoto, N. et al. Increased expression of interleukin-17 is associated with macrophages in chronic immune thrombocytopenia. Int. J. Clin. Exp. Pathol. 11, 2419\u20132429 (2018).","journal-title":"Int. J. Clin. Exp. Pathol."}],"updated-by":[{"DOI":"10.1038\/s41598-025-08742-4","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-59493-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-59493-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-59493-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T19:43:38Z","timestamp":1757101418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-59493-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,19]]},"references-count":74,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["59493"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-59493-7","relation":{"correction":[{"id-type":"doi","id":"10.1038\/s41598-025-08742-4","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,19]]},"assertion":[{"value":"3 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2025","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-025-08742-4","URL":"https:\/\/doi.org\/10.1038\/s41598-025-08742-4","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"9040"}}