{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T21:35:10Z","timestamp":1771018510909,"version":"3.50.1"},"reference-count":8,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,4,25]],"date-time":"2008-04-25T00:00:00Z","timestamp":1209081600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis & Rheumatism"],"published-print":{"date-parts":[[2008,5]]},"abstract":"Abstract<\/jats:title>Objective<\/jats:title>Antineutrophil cytoplasmic antibodies (ANCA) binding to neutrophil elastase (NE) and proteinase 3 (PR3) are detectable in most patients with cocaine\u2010induced midline destructive lesions (CIMDL), but the pathogenic role and antigen specificity of these antibodies are unknown. This study was undertaken to assess the effects of NE ANCA on the enzymatic activity of NE, to determine whether these antibodies interfere with the physiologic effect of secretory leukoprotease inhibitor (SLPI), and to investigate the antigen specificity of both NE and PR3 ANCA in patients with CIMDL. We also compared the binding of PR3 ANCA in patients with CIMDL with that in patients with Wegener's granulomatosis (WG).<\/jats:p><\/jats:sec>Methods<\/jats:title>PR3 ANCA and NE ANCA were detected by capture enzyme\u2010linked immunosorbent assays (ELISAs) and by indirect immunofluorescence. IgG was purified from the patients' sera, and the influence of NE ANCA on the enzymatic activity of NE and on the inhibitory activity of SLPI was investigated by determining the hydrolysis of N<\/jats:italic>\u2010methoxysuccinyl\u2010Ala\u2010Ala\u2010Pro\u2010Val p<\/jats:italic>\u2010nitroanilide by NE.<\/jats:p><\/jats:sec>Results<\/jats:title>IgG from NE ANCA\u2013positive sera of patients with CIMDL inhibited the enzymatic activity of NE and did not interfere with the activity of SLPI. In contrast to the findings in WG sera, measurement of PR3 ANCA in CIMDL sera showed only fair to moderate concordance between the 2 different capture ELISAs. Cross\u2010inhibition experiments demonstrated that NE ANCA and PR3 ANCA represent distinct autoantibodies in patients with CIMDL.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The functional effects of NE ANCA on the enzymatic activity of NE or on the activity of SLPI cannot be implicated in the pathogenesis of CIMDL. The autoimmune reaction that targets neutrophil serine proteases in patients with CIMDL is frequently directed against more than one antigen. The ANCA response, including the reactivity of PR3 ANCA, in patients with CIMDL differs from what has been described in patients with WG.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.23469","type":"journal-article","created":{"date-parts":[[2008,4,25]],"date-time":"2008-04-25T20:17:11Z","timestamp":1209154631000},"page":"1546-1551","source":"Crossref","is-referenced-by-count":48,"title":["Functional characterization of antineutrophil cytoplasmic antibodies in patients with cocaine\u2010induced midline destructive lesions"],"prefix":"10.1002","volume":"58","author":[{"given":"Tobias","family":"Peikert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier D.","family":"Finkielman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber M.","family":"Hummel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen E.","family":"McKenney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gina","family":"Gregorini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Trimarchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Specks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,4,25]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20479"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.1998.v31.pm9631842"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115021"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(97)00203-2"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2005.09.004"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/194589240602000207"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2000.01410.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64532-4"}],"container-title":["Arthritis & Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.23469","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.23469","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T23:31:31Z","timestamp":1698708691000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.23469"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,4,25]]},"references-count":8,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2008,5]]}},"alternative-id":["10.1002\/art.23469"],"URL":"https:\/\/doi.org\/10.1002\/art.23469","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,4,25]]}}}