{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T10:12:47Z","timestamp":1777975967346,"version":"3.51.4"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["EMIDDT"],"published-print":{"date-parts":[[2026,4,30]]},"abstract":"\n Introduction:<\/jats:title>\n The role of Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing\nLigand (TRAIL) has been highlighted in autoimmune and metabolic disorders. However, there is\nstill an inadequate explanation of its causal relationship with primary immune thrombocytopenia\n(ITP). This study employed Mendelian Randomization (MR) to identify the potential causal associations among TRAIL, plasma metabolites, and ITP.<\/jats:p>\n <\/jats:sec>\n \n Method:<\/jats:title>\n This study was conducted focusing on analyzing data from a Genome-Wide Association\nStudy (GWAS) comprising inflammatory proteins, plasma metabolites, and the FinnGen consortium. The Inverse Variance Weighted (IVW) method was adopted to derive the causal estimates primarily. Sensitivity analyses included Cochran\u2019s Q test for heterogeneity, MR-Egger regression for\nhorizontal pleiotropy, leave-one-out analysis, and validation via Bayesian Weighted MR (BWMR). In addition, the identification and quantification of potential mediating metabolites were realized through a two-step MR approach.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Genetically predicted higher TRAIL levels were associated with a reduced risk of ITP\n(IVW odds ratio [OR] = 0.78, 95% confidence interval [CI]: 0.65\u20130.92, P = 0.0042), which was\nconfirmed by BWMR (OR = 0.77, 95% CI: 0.65\u20130.92, P = 0.0043). Reverse MR analysis revealed no significant causal effect of ITP on TRAIL. Among the 48 plasma metabolites causally\nassociated with TRAIL, only 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME) exhibited a significant association with ITP in BWMR (OR = 0.75, 95% CI: 0.58\u20130.97, P = 0.0316). Mediation\nanalysis suggested that 12,13-DiHOME might partially mediate the effect of TRAIL on ITP, with\nan exploratory estimated mediation proportion of 7.55%.<\/jats:p>\n <\/jats:sec>\n \n Discussion:<\/jats:title>\n Mediation analysis revealed that 12,13-DiHOME mediated 7.55% of the TRAIL-related ITP risk reduction. These findings provide preliminary evidence supporting a potential mediating role of 12,13-DiHOME in the protective effect of TRAIL against ITP, suggesting the existence of an immunometabolic pathway linking TRAIL to ITP pathogenesis.<\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n This MR study provides genetic evidence of the potentially protective causal effect\nof TRAIL against ITP, which may be mediated partially by 12,13-DiHOME. Our findings may\nhighlight a novel immunometabolic pathway in ITP pathogenesis, meriting further investigation<\/jats:p>\n <\/jats:sec>","DOI":"10.2174\/0118715303462239260413042004","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T09:24:51Z","timestamp":1777973091000},"update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetically Predicted 12,13-DiHOME Mediates the\nAssociation between TNF-Related ApoptosisInducing Ligand and Immune Thrombocytopenia"],"prefix":"10.2174","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7418-9334","authenticated-orcid":true,"given":"Chendong","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7550-147X","authenticated-orcid":true,"given":"Yiwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5318-4323","authenticated-orcid":true,"given":"Jun","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4861-0759","authenticated-orcid":true,"given":"Yang","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7478-561X","authenticated-orcid":true,"given":"Zhanyan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8894-6643","authenticated-orcid":true,"given":"Zhan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8807-6565","authenticated-orcid":true,"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","container-title":["Endocrine, Metabolic & Immune Disorders - Drug Targets"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/0118715303462239260413042004","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/253213\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/article\/download?doi=10.2174\/0118715303462239260413042004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T09:25:13Z","timestamp":1777973113000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/253213\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":0,"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/0118715303462239260413042004","relation":{},"ISSN":["1871-5303"],"issn-type":[{"value":"1871-5303","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Double blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2025-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-29","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}