{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T22:28:53Z","timestamp":1783031333274,"version":"3.54.6"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Activated neutrophils release neutrophil extracellular traps (NETs), resulting in a form of cell death called NETosis. NET formation is reportedly involved in the onset of systemic lupus erythematosus and antineutrophil cytoplasmic antibody (ANCA)\u2010associated vasculitis (AAV). Citrullination of histones is a key step in NET formation, and the presence of citrullinated histones in neutrophils may be associated with disease induction and activity. The aim of this study was to investigate the relationship between infiltrating citrullinated histone H3 (H3Cit)\u2010positive neutrophils and disease specificity and activity in various glomerulonephritides.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We selected 32 kidney biopsies with glomerulonephritides, including AAV, lupus nephritis (LN), Henoch\u2013Sch\u00f6nlein purpura nephritis (HSPN), and poststreptococcal acute glomerulonephritis (PSAGN). We examined the presence of H3Cit in infiltrating neutrophils and their association with necrotising, crescentic lesions and tubulointerstitial lesions. In PSAGN and HSPN, we found many myeloperoxidase (MPO)+ neutrophils in glomeruli; however, only a few were H3Cit+. In LN, MPO+ neutrophils mainly existed in the margins of glomerular tufts forming wire\u2010loop lesions, and some of these were noted to be H3Cit+ neutrophils. In contrast, we found a significantly higher frequency of H3Cit+ neutrophils, despite the small number of MPO+ neutrophils, in microscopic polyangiitis in AAV. In particular, H3Cit+ neutrophils were prominent in necrotising lesions along the glomerular capillaries. Moreover, we also found H3Cit+ neutrophils in the interstitium, with marked peritubular capillaritis in AAV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>H3Cit immunostaining is a useful tool for identifying activated neutrophils. The frequency of H3Cit+ neutrophils is not only a disease\u2010specific marker but also a potential marker for disease activity in AAV.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14247","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T21:22:17Z","timestamp":1600723337000},"page":"520-531","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Immunohistochemical detection of citrullinated histone H3\u2010positive neutrophils is useful for identifying active glomerular and interstitial lesions in antineutrophil cytoplasmic antibody\u2010associated vasculitis"],"prefix":"10.1111","volume":"78","author":[{"given":"Hidehito","family":"Kimura","sequence":"first","affiliation":[{"name":"Department of Nephrology Nippon Medical School  Tokyo 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