{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:44:06Z","timestamp":1791999846398,"version":"4.4.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovation Project of Guangxi Graduate Education","award":["NO: YCBZ2021047"],"award-info":[{"award-number":["NO: YCBZ2021047"]}]},{"name":"Research Basic Ability Enhancement Project of Young and Middle-aged Teachers in Guangxi Universities","award":["2021KY0096"],"award-info":[{"award-number":["2021KY0096"]}]},{"DOI":"10.13039\/100001406","name":"Guangxi Medical High-level Backbone Talent \"139\" Plan","doi-asserted-by":"publisher","award":["G201901010"],"award-info":[{"award-number":["G201901010"]}],"id":[{"id":"10.13039\/100001406","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Key Laboratory of Children's Disease Research in Guangxi\u2019s Colleges and Universities, Education Department of Guangxi Zhuang Autonomous Region."},{"name":"Excellent Medical Talents Training Program of the First Affiliated Hospital of Guangxi Medical University"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Neutrophil extracellular traps (NETs) have been found to play a role in the development of autoimmune diseases. In the past two years, studies have demonstrated a significantly increase of NETs in skin tissues during the early stages of IgAV, indicating their involvement in disease activity among children with IgAV. However, the presence of NETs in IgAV animal models has not yet been reported. The objective of this study is to investigate whether NETs are involved in the pathogenesis of IgA vasculitis (IgAV) rats.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Twenty-four SD rats were randomly divided into three groups: the ovalbumin group, the gliadin group, and the control group. The IgAV rat models were established administering Indian ink with ovalbumin (ovalbumin group) or gliadin (gliadin group) with Freund\u2019s complete adjuvant. The cell-free DNA (cf-DNA) was quantified by using dsDNA quantification kit, while the levels of Immunoglobulins, complement C3 and myeloperoxidase-DNA (MPO-DNA) in serum were tested using enzyme linked immunosorbent assay (ELISA). The IgA, complement C3 and NETs in tissues were detected through multiple immunofluorescences.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Both the ovalbumin group and gliadin group showed IgA and C3 deposition in various tissues, including the glomerular mesangial region, skin, and digestive tract, while the control group showed no such deposition. The levels of circulatory cf-DNA and MPO-DNA, which are components of NETs, were significantly elevated in both ovalbumin and gliadin groups compared with the control group. Furthermore, the presence of NETs were found in gastrointestinal and renal tissues of the ovalbumin and gliadin groups, but not in the control group.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>IgAV model rat can be established through the combination of ovalbumin and gliadin with Indian ink and Freund\u2019s complete adjuvant. This study provides the first confirmation that NETs are involved in the pathogenesis of IgAV rat.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0288538","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T17:37:01Z","timestamp":1689961021000},"page":"e0288538","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neutrophil extracellular traps involved in the pathogenesis of IgA vasculitis: Confirmed in two IgAV rat models"],"prefix":"10.1371","volume":"18","author":[{"given":"Xiu-Qi","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Sen","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5463-8048","authenticated-orcid":true,"given":"Yuan-Han","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"key":"pone.0288538.ref001","doi-asserted-by":"crossref","first-page":"421","DOI":"10.3389\/fped.2018.00421","article-title":"Childhood Vasculitis","volume":"6","author":"A Schnabel","year":"2018","journal-title":"Front Pediatr"},{"issue":"4","key":"pone.0288538.ref002","doi-asserted-by":"crossref","first-page":"265","DOI":"10.2174\/18756336MTA2lNDYc2","article-title":"Henoch-Schonlein Purpura in Children: An Updated Review","volume":"16","author":"AKC Leung","year":"2020","journal-title":"Curr Pediatr Rev"},{"key":"pone.0288538.ref003","doi-asserted-by":"crossref","first-page":"771619","DOI":"10.3389\/fimmu.2021.771619","article-title":"Pathogenesis of IgA Vasculitis: An Up-To-Date Review","volume":"12","author":"Y Song","year":"2021","journal-title":"Front Immunol"},{"key":"pone.0288538.ref004","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3389\/fped.2019.00257","article-title":"Childhood IgA Vasculitis (Henoch Schonlein Purpura)-Advances and Knowledge Gaps","volume":"7","author":"L Oni","year":"2019","journal-title":"Front Pediatr"},{"issue":"3","key":"pone.0288538.ref005","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.autrev.2017.11.024","article-title":"Genetics of immunoglobulin-A vasculitis (Henoch-Schonlein purpura): An updated review","volume":"17","author":"R Lopez-Mejias","year":"2018","journal-title":"Autoimmun Rev"},{"issue":"12","key":"pone.0288538.ref006","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.autrev.2017.10.009","article-title":"New insights in the pathogenesis of immunoglobulin A vasculitis","volume":"16","author":"MH Heineke","year":"2017","journal-title":"Autoimmun Rev"},{"issue":"2","key":"pone.0288538.ref007","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00467-017-3597-4","article-title":"Vasculitis update: pathogenesis and biomarkers","volume":"33","author":"P Brogan","year":"2018","journal-title":"Pediatr Nephrol"},{"issue":"4","key":"pone.0288538.ref008","first-page":"3924","article-title":"Correlation between serum inflammatory factors TNF-alpha, IL-8, IL-10 and Henoch-Schonlein purpura with renal function impairment","volume":"15","author":"L Yuan","year":"2018","journal-title":"Exp Ther Med"},{"issue":"5663","key":"pone.0288538.ref009","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"V Brinkmann","year":"2004","journal-title":"Science"},{"issue":"4","key":"pone.0288538.ref010","doi-asserted-by":"crossref","first-page":"915","DOI":"10.3390\/cells9040915","article-title":"Neutrophil Extracellular Traps (NETs) Take the Central Stage in Driving Autoimmune Responses","volume":"9","author":"E Fousert","year":"2020","journal-title":"Cells"},{"issue":"11","key":"pone.0288538.ref011","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.autrev.2017.09.012","article-title":"Neutrophil extracellular traps (NETs) in autoimmune diseases: A comprehensive review","volume":"16","author":"KH Lee","year":"2017","journal-title":"Autoimmun Rev"},{"issue":"4","key":"pone.0288538.ref012","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.ajpath.2019.01.007","article-title":"Formation and Disordered Degradation of Neutrophil Extracellular Traps in Necrotizing Lesions of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis","volume":"189","author":"S Masuda","year":"2019","journal-title":"Am J Pathol"},{"issue":"17","key":"pone.0288538.ref013","first-page":"adv00281","article-title":"Neutrophil Extracellular Traps are Present in Immune-complex-mediated Cutaneous Small Vessel Vasculitis and Correlate with the Production of Reactive Oxygen Species and the Severity of Vessel Damage","volume":"100","author":"C Bergqvist","year":"2020","journal-title":"Acta Derm Venereol"},{"key":"pone.0288538.ref014","doi-asserted-by":"crossref","first-page":"668974","DOI":"10.3389\/fimmu.2021.668974","article-title":"The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis","volume":"12","author":"XQ Chen","year":"2021","journal-title":"Front Immunol"},{"issue":"1","key":"pone.0288538.ref015","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1159\/000519869","article-title":"Elevated Myeloperoxidase-DNA Complex Levels in Sera of Patients with IgA Vasculitis","volume":"89","author":"S Takeuchi","year":"2022","journal-title":"Pathobiology"},{"key":"pone.0288538.ref016","doi-asserted-by":"crossref","first-page":"8862","DOI":"10.1038\/srep08862","article-title":"Hematologic and immunological characteristics of Henoch-Schonlein purpura in rat and rabbit models induced with ovalbumin based on type III hypersensitivity","volume":"5","author":"Y Li","year":"2015","journal-title":"Sci Rep"},{"issue":"9","key":"pone.0288538.ref017","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1016\/j.mayocp.2019.04.034","article-title":"Clinical Characteristics of Biopsy-Proven IgA Vasculitis in Children and Adults: A Retrospective Cohort Study","volume":"94","author":"M Villatoro-Villar","year":"2019","journal-title":"Mayo Clin Proc"},{"issue":"1","key":"pone.0288538.ref018","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s42358-019-0064-x","article-title":"The profile and clinical outcomes of patients with renal involvement due to IgA vasculitis: is azathioprine a good option for treatment?","volume":"59","author":"V Schinzel","year":"2019","journal-title":"Adv Rheumatol"},{"key":"pone.0288538.ref019","article-title":"Hemotological Indices for Predicting Internal Organ Involvement in Henoch-Schonlein Purpura","author":"ZC Ozdemir","year":"2019","journal-title":"J Pediatr Hematol Oncol"},{"issue":"3","key":"pone.0288538.ref020","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1006\/clin.1997.4493","article-title":"Is there IgA from gut mucosal origin in the serum of children with Henoch-Schonlein purpura?","volume":"86","author":"P Moja","year":"1998","journal-title":"Clin Immunol Immunopathol"},{"key":"pone.0288538.ref021","doi-asserted-by":"crossref","first-page":"3230","DOI":"10.1038\/ncomms4230","article-title":"A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages","volume":"5","author":"Y Yu","year":"2014","journal-title":"Nat Commun"},{"issue":"10","key":"pone.0288538.ref022","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1007\/s00251-003-0626-1","article-title":"Identification of the rat IgA Fc receptor encoded in the leukocyte receptor complex","volume":"55","author":"T Maruoka","year":"2004","journal-title":"Immunogenetics"},{"issue":"2","key":"pone.0288538.ref023","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1084\/jem.157.2.572","article-title":"Experimental IgA nephropathy induced by oral immunization","volume":"157","author":"SN Emancipator","year":"1983","journal-title":"J Exp Med"},{"issue":"14","key":"pone.0288538.ref024","doi-asserted-by":"crossref","DOI":"10.3390\/jcm10143142","article-title":"History of IgA Nephropathy Mouse Models","volume":"10","author":"B Wehbi","year":"2021","journal-title":"J Clin Med"},{"issue":"1","key":"pone.0288538.ref025","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ki.1987.1","article-title":"Experimental models for IgA-associated nephritis","volume":"31","author":"A. Rifai","year":"1987","journal-title":"Kidney Int"},{"key":"pone.0288538.ref026","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3389\/fimmu.2016.00117","article-title":"The Origin and Activities of IgA1-Containing Immune Complexes in IgA Nephropathy","volume":"7","author":"B Knoppova","year":"2016","journal-title":"Front Immunol"},{"issue":"5","key":"pone.0288538.ref027","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s00345-007-0192-5","article-title":"Urinary biomarkers of IgA nephropathy and other IgA-associated renal diseases","volume":"25","author":"BA Julian","year":"2007","journal-title":"World J Urol"},{"issue":"8","key":"pone.0288538.ref028","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/s41379-019-0259-z","article-title":"Complement-mediated microangiopathy in IgA nephropathy and IgA vasculitis with nephritis","volume":"32","author":"JS Chua","year":"2019","journal-title":"Mod Pathol"},{"issue":"7","key":"pone.0288538.ref029","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1177\/0300060518775814","article-title":"IgA nephropathy with leucocytoclastic vasculitis","volume":"46","author":"LY Wei","year":"2018","journal-title":"J Int Med Res"},{"issue":"3","key":"pone.0288538.ref030","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.kint.2017.10.019","article-title":"IgA nephropathy and IgA vasculitis with nephritis have a shared feature involving galactose-deficient IgA1-oriented pathogenesis","volume":"93","author":"H Suzuki","year":"2018","journal-title":"Kidney Int"},{"key":"pone.0288538.ref031","article-title":"Neutrophil Extracellular Traps (NETs) profiles in patients with incident SLE and lupus nephritis","author":"M Bruschi","year":"2019","journal-title":"J Rheumatol"},{"issue":"6","key":"pone.0288538.ref032","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.jid.2018.11.021","article-title":"Neutrophil Extracellular Traps Induce Human Th17 Cells: Effect of Psoriasis-Associated TRAF3IP2 Genotype","volume":"139","author":"S Lambert","year":"2019","journal-title":"J Invest Dermatol"},{"key":"pone.0288538.ref033","doi-asserted-by":"crossref","first-page":"102484","DOI":"10.1016\/j.jaut.2020.102484","article-title":"Autoantibodies to neutrophil extracellular traps represent a potential serological biomarker in rheumatoid arthritis","volume":"113","author":"CM de Bont","year":"2020","journal-title":"J Autoimmun"},{"key":"pone.0288538.ref034","doi-asserted-by":"crossref","first-page":"256","DOI":"10.3389\/fimmu.2016.00256","article-title":"Neutrophil Extracellular Traps in ANCA-Associated Vasculitis","volume":"7","author":"D Soderberg","year":"2016","journal-title":"Front Immunol"},{"key":"pone.0288538.ref035","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/978-1-4939-0326-9_11","article-title":"Detection of SLE antigens in neutrophil extracellular traps","volume":"1134","author":"C Carmona-Rivera","year":"2014","journal-title":"Methods Mol Biol"},{"issue":"1","key":"pone.0288538.ref036","first-page":"66","article-title":"Degradation of neutrophil extracellular traps is decreased in patients with antiphospholipid syndrome","volume":"32","author":"J Leffler","year":"2014","journal-title":"Clin Exp Rheumatol"},{"issue":"5","key":"pone.0288538.ref037","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s10157-012-0738-8","article-title":"Possible implication of disordered neutrophil extracellular traps in the pathogenesis of MPO-ANCA-associated vasculitis","volume":"17","author":"D Nakazawa","year":"2013","journal-title":"Clin Exp Nephrol"},{"issue":"11","key":"pone.0288538.ref038","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1002\/art.34619","article-title":"Abnormal conformation and impaired degradation of propylthiouracil-induced neutrophil extracellular traps: implications of disordered neutrophil extracellular traps in a rat model of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis","volume":"64","author":"D Nakazawa","year":"2012","journal-title":"Arthritis Rheum"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0288538","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T17:37:50Z","timestamp":1689961070000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0288538"}},"subtitle":[],"editor":[{"given":"Fabio","family":"Sallustio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,7,21]]},"references-count":38,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0288538","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,21]]}}}