{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T09:29:27Z","timestamp":1772789367395,"version":"3.50.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"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:p>\n                    Ankylosing spondylitis (AS) is a chronic immune-mediated arthritis marked by persistent inflammation and progressive structural damage. Although dysregulation of programmed cell death (PCD) is increasingly recognized in AS pathogenesis, the full spectrum of transcript-level regulation remains unclear. Here, we employed Oxford Nanopore Technologies (ONT) long-read RNA sequencing to comprehensively profile peripheral blood transcriptomes from six AS patients and six matched healthy controls. Our analysis identified 1,088 differentially expressed genes (DEGs) and 1,812 differentially expressed transcripts (DETs), with upregulated transcripts enriched in apoptosis, autophagy, and transcriptional regulation. We further detected 50 transcripts with significant differential usage and 304 alternative splicing events affecting immune- and PCD-related genes, including\n                    <jats:italic>FCGR2B<\/jats:italic>\n                    ,\n                    <jats:italic>TLR2<\/jats:italic>\n                    , and\n                    <jats:italic>STAT5B<\/jats:italic>\n                    . Integrative multilayered analysis revealed 26 core genes, such as\n                    <jats:italic>NAMPT<\/jats:italic>\n                    ,\n                    <jats:italic>GATA2<\/jats:italic>\n                    , and\n                    <jats:italic>DDIT3<\/jats:italic>\n                    , showing consistent dysregulation at gene, isoform, and splicing levels, highlighting convergent regulatory networks underlying immune imbalance and cell death in AS. These findings provide the first isoform-resolved transcriptomic landscape of PCD regulation in AS, which unveils extensive regulatory complexity and nominates a set of core genes for future mechanistic and therapeutic exploration.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1640271","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:42:58Z","timestamp":1772779378000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated long-read transcriptomic profiling of peripheral blood from ankylosing spondylitis patients identifies regulatory shifts and core genes associated with programmed cell death"],"prefix":"10.3389","volume":"17","author":[{"given":"Xue","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, People\u2019s Hospital of Henan University","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panlong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, People\u2019s Hospital of Henan University","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoran","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Emergency, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, People\u2019s Hospital of Henan University","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Nursing Department, Air Force Medical Center, PLA","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lipu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, People\u2019s Hospital of Henan University","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Chen","sequence":"additional","affiliation":[{"name":"Wuhan Ruixing Biotechnology Co., Ltd.","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianshu","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, People\u2019s Hospital of Henan University","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanwei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Emergency, Henan Provincial People\u2019s Hospital, People\u2019s Hospital of Zhengzhou University, People\u2019s Hospital of Henan University","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"B1","article-title":"Ankylosing spondylitis: an update","volume":"42","author":"Golder","year":"2013","journal-title":"Aust Fam Physician"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket387","article-title":"Global prevalence of ankylosing spondylitis","volume":"53","author":"Dean","year":"2014","journal-title":"Rheumatol (Oxford)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1015182","article-title":"IL-17A and TNF-\u03b1 inhibitors induce multiple molecular changes in 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