{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:11:18Z","timestamp":1789607478290,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62071011"],"award-info":[{"award-number":["62071011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alterations of the trimethylation of histone\u00a03\u00a0lysine 4 (H3K4me3) mark in monocytes are implicated in the development of autoimmune diseases. Therefore, the purpose of our study was to elucidate the role of H3K4me3\u2010mediated epigenetics in the pathogenesis of antiphospholipid syndrome (APS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>H3K4me3 Cleavage Under Targets and Tagmentation and Assay for Transposase\u2010Accessible Chromatin were performed to determine the epigenetic profiles. Luciferase reporter assay, RNA immunoprecipitation, RNA pull\u2010down, co\u2010immunoprecipitation and chromatin immunoprecipitation were performed for mechanistic studies. Transmission electron microscopy and propidium iodide staining confirmed cell pyroptosis. Primary monocytes from patients with primary APS (PAPS) and healthy donors were utilised to test the levels of key molecules. A mouse model mimicked APS was constructed with beta2\u2010glycoprotein I (\u03b22GPI) injection. Blood velocity was detected using murine Doppler ultrasound.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>H3K4me3 signal and open chromatin at the <jats:italic>ARID5B<\/jats:italic> promoter were increased in an in vitro model of APS. The epigenetic factor ARID5B directly activated LINC01128 transcription at its promoter. LINC01128 promoted the formation of the BTF3\/STAT3 complex to enhance STAT3 phosphorylation. Activated STAT3 interacted with the <jats:italic>NLRP3<\/jats:italic> promoter and subsequently stimulated pyroptosis and apoptosis. ARID5B or BTF3 depletion compensated for LINC01128\u2010induced pyroptosis and apoptosis by inhibiting STAT3 phosphorylation. In mice with APS, \u03b22GPI exposure elevated the levels of key proteins of pyroptosis and apoptosis pathways in bone marrow\u2010derived monocytes, reduced the blood velocity of the ascending aorta, increased the thrombus size of the carotid artery, and promoted the release of interleukin (IL)\u201018, IL\u20101\u03b2 and tissue factor. Patients with PAPS had the high\u2010expressed ARID5B and LINC01128, especially those with triple positivity for antiphospholipid antibodies. Moreover, there was a positive correlation between ARID5B and LINC01128 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study indicated that ARID5B\/LINC01128 was synergistically upregulated in APS, and they aggravated disease pathogenesis by enhancing the formation of the BTF3\/STAT3 complex and boosting p\u2010STAT3\u2010mediated pyroptosis and apoptosis, thereby providing candidate therapeutic targets for APS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The H3K4me3 mark and chromatin accessibility at the <jats:italic>ARID5B<\/jats:italic> promoter are increased in vitro model mimicked APS.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ARID5B\u2010mediated LINC01128 induces pyroptosis and apoptosis via p\u2010STAT3 by binding to BTF3.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ARID5B is high\u2010 expressed in patients with primary APS and positively correlated with LINC01128 expression.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>OICR\u20109429 treatment mitigates pyroptosis and related inflammation in vivo and in vitro models mimicked APS.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1539","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T12:00:16Z","timestamp":1705320016000},"source":"Crossref","is-referenced-by-count":8,"title":["ARID5B\u2010mediated LINC01128 epigenetically activated pyroptosis and apoptosis by promoting the formation of the BTF3\/STAT3 complex in \u03b22GPI\/anti\u2010\u03b22GPI\u2010treated monocytes"],"prefix":"10.1002","volume":"14","author":[{"given":"Yuan","family":"Tan","sequence":"first","affiliation":[{"name":"Institute of Medical Technology Peking University Health Science Center  Beijing China"},{"name":"Department of Laboratory Medicine Peking University Third Hospital  Beijing 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