{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:43:58Z","timestamp":1789767838146,"version":"4.0.1"},"reference-count":63,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR041199"],"award-info":[{"award-number":["AR041199"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp;amp; Rheumatology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Neutrophil dysfunction is a hallmark of systemic lupus erythematosus (SLE), but its molecular basis remains unclear. This study explores transcriptional and posttranscriptional changes in low\u2010density granulocytes (LDGs), a proinflammatory neutrophil subset expanded in SLE, focusing on NADPH oxidase (Nox) function and minor intron splicing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      LDGs and normal\u2010density granulocytes (NDGs) were isolated from patients with SLE and healthy controls (HCs). CYBA (p22\n                      <jats:sup>phox<\/jats:sup>\n                      ) expression was evaluated at transcript and protein levels. Nox activity was measured using luminol assays. Bulk RNA sequencing (RNA\u2010seq) and rMATS software were used to assess alternative splicing, particularly of U12\u2010type intron\u2010containing genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CYBA expression was reduced in SLE LDGs (n\u00a0=\u00a011) compared to SLE and HC NDGs (n\u00a0=\u00a06), with levels resembling those in chronic granulomatous disease neutrophils. SLE LDGs exhibited impaired Nox activity (n\u00a0=\u00a07 SLE, n\u00a0=\u00a012 HC). CYBA is a U12 intron\u2010containing gene, and transcriptomic analysis revealed broad down\u2010regulation of this gene class in SLE LDGs, suggesting minor spliceosome dysfunction. rMATS analysis showed increased U12\u2010type intron retention and widespread splicing defects\u2014including exon skipping and mutually exclusive exon use\u2014in genes such as\n                      <jats:italic>GBP5<\/jats:italic>\n                      ,\n                      <jats:italic>MAEA<\/jats:italic>\n                      , and\n                      <jats:italic>STX10<\/jats:italic>\n                      . These abnormalities were validated in an independent long\u2010read RNA\u2010seq data set from SLE peripheral blood mononuclear cells. Importantly, splicing disruptions correlated with disease activity and autoantibody profiles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Impaired U12\u2010dependent splicing may contribute to neutrophil dysfunction in SLE, potentially via defective oxidative burst and altered immune regulation. These findings highlight the minor spliceosome as a novel player in lupus pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70053","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T14:34:37Z","timestamp":1768228477000},"page":"1490-1499","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dysregulation of\n                    <scp>U12<\/scp>\n                    \u2010Type Splicing in Lupus Neutrophils"],"prefix":"10.1002","volume":"78","author":[{"given":"Luz P.","family":"Blanco","sequence":"first","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binod","family":"Regmi","sequence":"additional","affiliation":[{"name":"Biodata Mining and Discovery Section, Office of Science and Technology, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7706-1464","authenticated-orcid":false,"given":"Carmelo","family":"Carmona\u2010Rivera","sequence":"additional","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudong","family":"Liu","sequence":"additional","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiantao","family":"Wang","sequence":"additional","affiliation":[{"name":"RNA Molecular Biology Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip M.","family":"Carlucci","sequence":"additional","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2756-161X","authenticated-orcid":false,"given":"Monica M.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zerai","family":"Manna","sequence":"additional","affiliation":[{"name":"Lupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarfaraz","family":"Hasni","sequence":"additional","affiliation":[{"name":"Lupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hafner","sequence":"additional","affiliation":[{"name":"RNA Molecular Biology Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2010Wei","family":"Sun","sequence":"additional","affiliation":[{"name":"Biodata Mining and Discovery Section, Office of Science and Technology, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana J.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"},{"name":"Lupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0000000000002209"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/6.8.1097"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X211032457"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.4.2297"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/13.9.1155"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-018-8718-8"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keab279"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13071257"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23763"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2024.100654"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-091719-064225"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-025-00846-x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.06.008"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.080337.124"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10123466"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2015.3"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202451508"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109339"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020106536"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19451-z"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.260562"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7042"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1513"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.130574"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408360290795574"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.091660"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.112434"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90532-U"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2017.06.009"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11930"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00787-0"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13161"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4027"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406486200"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.305280"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5828"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41128"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400928"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.10.019"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419161111"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1455616"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.90"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2005.1.89"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.639321"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20177728"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008708"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2025.1575862"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/08820139.2022.2122834"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.15586\/aei.v52i6.1188"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.184739"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07620-0"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf297"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.00780"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-019-00603-w"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113251108"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt532"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.639021"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12953"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908576116"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07458-7"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2009.27"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70053","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.70053","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70053","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T15:25:23Z","timestamp":1782746723000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.70053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,19]]},"references-count":63,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/art.70053"],"URL":"https:\/\/doi.org\/10.1002\/art.70053","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.11.06.686965","asserted-by":"object"}]},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,19]]},"assertion":[{"value":"2025-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}