{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T18:09:56Z","timestamp":1757700596424,"version":"3.33.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,9,27]],"date-time":"2007-09-27T00:00:00Z","timestamp":1190851200000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract<\/jats:sc>:\u2002<\/jats:bold><jats:bold>Conventional immunosuppressive treatment of systemic vasculitides has improved their often fatal outcome, but is burdened by cytotoxic side effects and frequent relapses. Recent advances in the therapy of systemic vasculitides with biologicals have helped to establish new options for patients resistant to conventional treatment. Moreover, early intervention aiming to interfere with specific targets important in the break of tolerance and\/or persistence of the autoimmune response might further improve the prognosis of autoimmune vasculitides such as antineutrophil cytoplasmic autoantibody (ANCA)\u2010associated vasculitides (AAV).<jats:italic>In vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>studies suggest that the interaction of ANCA and cytokine (TNF\u2010\u03b1, IL\u20101)\u2010primed neutrophils results in premature neutrophil activation and degranulation, subsequent endothelial cell damage, and further leukocyte recruitment. For one of the AAV, Wegener's granulomatosis, recent<jats:italic>ex vivo<\/jats:italic>data have provided evidence that WG\u2010granulomata might provide the necessary \u201cproinflammatory environment\u201d for the break of tolerance and display features of lymphoid\u2010like tissue neoformation, in which autoimmunity to \u201cWegener's autoantigen\u201d proteinase 3 PR3 could be sustained. Blocking TNF\u2010\u03b1 and eliminating autoreactive B cells seem promising treatment targets to interfere with these fundamental disease processes. While the recombinant TNF\u2010\u03b1 receptor\/IgG1 fusion protein etanercept, in addition to standard therapy with subsequent tapering of standard medications, was found to be not effective for maintenance of remission, open clinical studies suggest a beneficial effect of the anti\u2010TNF\u2010\u03b1 antibody infliximab in addition to standard therapy for the induction of remission in patients with refractory AAV. Peripheral B cell depletion with the anti\u2010CD20 antibody rituximab also induced remissions in AAV in uncontrolled trials.<\/jats:bold><\/jats:p>","DOI":"10.1196\/annals.1423.028","type":"journal-article","created":{"date-parts":[[2007,10,2]],"date-time":"2007-10-02T20:20:20Z","timestamp":1191356420000},"page":"261-270","source":"Crossref","is-referenced-by-count":12,"title":["Current State of Biologicals in the Management of Systemic Vasculitis"],"prefix":"10.1111","volume":"1110","author":[{"given":"PETER","family":"LAMPRECHT","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ANDREAS","family":"TILL","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00d6RG","family":"STEINMANN","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"PEER M.","family":"ARIES","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"WOLFGANG L.","family":"GROSS","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,9,27]]},"reference":[{"issue":"1","key":"e_1_2_9_2_2","first-page":"S47","article-title":"Immunopathology and new therapeutic considerations in ANCA\u2010associated vasculitides","volume":"3","author":"Gross W.L.","year":"2004","journal-title":"Autoimmun. 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