{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:39:10Z","timestamp":1793176750481,"version":"4.5.0"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801597"],"award-info":[{"award-number":["81801597"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHA2040\/1\u20101"],"award-info":[{"award-number":["SCHA2040\/1\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Gout flares that occur during urate\u2010lowering therapy (ULT) are typically related to the shrinkage of tophi due to aggregated neutrophil extracellular traps (NETs) that have captured monosodium urate crystals in the tissues. The present study was undertaken to analyze the blocking effect of \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010antitrypsin on neutrophil elastase, and it was found that \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010antitrypsin induced rapid inflammation in the presence of unstable tophi.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cell\u2010free DNA levels in serum samples were compared between patients who experienced a varying number of gout flares. We investigated whether cell\u2010free DNA in serum samples and \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010antitrypsin could be altered after the initiation of ULT. In mice, an injection of monosodium urate monohydrate (MSU) crystals was used to form a mimic of tophi in the peritoneal cavity, which was then analyzed using immunofluorescence staining. Finally, we investigated the relapse of inflammation by analyzing the levels of \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010antitrypsin in 2 kinds of artificial tophi and in tophus\u2010bearing mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Levels of cell\u2010free DNA in serum samples correlated with the number of flares experienced by patients with tophaceous gout. ULT induced an increase in cell\u2010free DNA in the serum of patients with tophi. Increases in levels of \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010antitrypsin were seen in patients with tophi who received ULT. Chalk\u2010like tophi removed from the peritoneal cavity of mice after MSU crystals induced inflammation showed abundant coexpression of interleukin\u20101\u03b2 (IL\u20101\u03b2) and IL\u20106\u2013associated NETs. A relapse in inflammation was induced by \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010antitrypsin during the spontaneous resolution of MSU crystal\u2013induced peritonitis. We observed that \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      \u2010antitrypsin blocks cytokine degradation by neutrophil elastase during the resolution phase of tophi.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ULT causes shrinkage of the tophi reflected by an increase in the levels of cell\u2010free DNA in serum. In the resolution phase of tophi in mice, NET\u2010associated neutrophil elastase degrades proinflammatory cytokines and, thus, ameliorates inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42431","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T01:31:47Z","timestamp":1672191107000},"page":"1039-1047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Neutrophil Extracellular Trap\u2013Borne Elastase Prevents Inflammatory Relapse in Intercritical Gout"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8315-742X","authenticated-orcid":false,"given":"Lei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Rheumatology the Second affiliated Hospital of Zhejiang University, School of Medicine  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhen","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology the Second affiliated Hospital of Zhejiang University, School of Medicine  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Department of Internal Medicine 3\u2010Rheumatology and Immunology Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg (FAU), Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Schauer","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Department of Internal Medicine 3\u2010Rheumatology and Immunology Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg (FAU), Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1277-5164","authenticated-orcid":false,"given":"Janina","family":"Schoen","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Immuntherapie (DZI), Department of Internal Medicine 3\u2010Rheumatology and Immunology Friedrich\u2010Alexander University Erlangen\u2010N\u00fcrnberg (FAU), Universit\u00e4tsklinikum Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology the Second affiliated Hospital of Zhejiang University, School of Medicine  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ci","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Zhejiang University School of Medicine Sir Run Run Shaw Hospital  Zhejiang 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