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Rheumatology"],"published-print":{"date-parts":[[2018,7]]},"abstract":"Objective<\/jats:title>To evaluate circulating cytokine profiles in patients with antineutrophil cytoplasmic antibody\u2013associated vasculitis (AAV<\/jats:styled-content>), classified by antineutrophil cytoplasmic antibody (ANCA<\/jats:styled-content>) specificity (proteinase 3 ANCA<\/jats:styled-content> [PR<\/jats:styled-content>3\u2010ANCA<\/jats:styled-content>] versus myeloperoxidase ANCA<\/jats:styled-content> [MPO<\/jats:styled-content>\u2010ANCA<\/jats:styled-content>]) or by clinical diagnosis (granulomatosis with polyangiitis [GPA<\/jats:styled-content>] versus microscopic polyangiitis [MPA<\/jats:styled-content>]).<\/jats:p><\/jats:sec>Methods<\/jats:title>A panel of 29 cytokines was tested in 186 patients with active AAV<\/jats:styled-content> at inclusion into the Rituximab in AAV<\/jats:styled-content> trial. Cytokine concentrations were compared between groups within each classification system. Multivariable analyses adjusted for age, sex, and renal insufficiency were performed, with each biomarker as a dependent variable and ANCA<\/jats:styled-content> specificity and clinical diagnosis as explanatory variables of interest.<\/jats:p><\/jats:sec>Results<\/jats:title>Levels of 9 circulating cytokines (interleukin\u20106 [IL<\/jats:styled-content>\u20106], granulocyte\u2013macrophage colony\u2010stimulating factor [GM<\/jats:styled-content>\u2010CSF<\/jats:styled-content>], IL<\/jats:styled-content>\u201015, IL<\/jats:styled-content>\u201018, CXCL<\/jats:styled-content>8\/IL<\/jats:styled-content>\u20108, CCL<\/jats:styled-content>\u201017\/thymus and activation\u2013regulated chemokine [TARC<\/jats:styled-content>], IL<\/jats:styled-content>\u201018 binding protein [IL<\/jats:styled-content>\u201018 BP<\/jats:styled-content>], soluble IL<\/jats:styled-content>\u20102 receptor \u03b1 [sIL<\/jats:styled-content>\u20102R\u03b1], and nerve growth factor \u03b2 [NGF<\/jats:styled-content>\u03b2]) were significantly higher in PR<\/jats:styled-content>3\u2010AAV<\/jats:styled-content> than MPO<\/jats:styled-content>\u2010AAV<\/jats:styled-content>, 4 cytokines (sIL<\/jats:styled-content>6R, soluble tumor necrosis factor receptor type II<\/jats:styled-content> [sTNFRII<\/jats:styled-content>], neutrophil gelatinase\u2013associated lipocalin [NGAL<\/jats:styled-content>], and soluble intercellular adhesion molecule 1 [sICAM<\/jats:styled-content>\u20101]) were higher in MPO<\/jats:styled-content>\u2010AAV<\/jats:styled-content> than in PR<\/jats:styled-content>3\u2010AAV<\/jats:styled-content>, 6 cytokines (IL<\/jats:styled-content>\u20106, GM<\/jats:styled-content>\u2010CSF<\/jats:styled-content>, IL<\/jats:styled-content>\u201015, IL<\/jats:styled-content>\u201018, sIL<\/jats:styled-content>\u20102R\u03b1, and NGF<\/jats:styled-content>\u03b2) were higher in GPA<\/jats:styled-content> than in MPA<\/jats:styled-content>, and 3 cytokines (osteopontin, sTNFRII<\/jats:styled-content>, and NGAL<\/jats:styled-content>) were higher in MPA<\/jats:styled-content> than in GPA<\/jats:styled-content> (all P<\/jats:italic> < 0.05). For nearly all cytokines, the difference between PR<\/jats:styled-content>3\u2010AAV<\/jats:styled-content> and MPO<\/jats:styled-content>\u2010AAV<\/jats:styled-content> was larger than that between GPA<\/jats:styled-content> and MPA<\/jats:styled-content>. The multivariate analysis showed that 8 cytokines (IL<\/jats:styled-content>\u201015, IL<\/jats:styled-content>\u20108, IL<\/jats:styled-content>\u201018 BP<\/jats:styled-content>, NGF<\/jats:styled-content>\u2010\u03b2, sICAM<\/jats:styled-content>\u20101, TARC<\/jats:styled-content>, osteopontin, and\u00a0kidney injury molecule 1 (P<\/jats:italic> < 0.05) distinguished patients with AAV<\/jats:styled-content> better (lower P<\/jats:italic> values and larger effect sizes) when grouped by ANCA<\/jats:styled-content> specificity than by clinical diagnosis.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Distinct cytokine profiles were identified for PR<\/jats:styled-content>3\u2010AAV<\/jats:styled-content> versus MPO<\/jats:styled-content>\u2010AAV<\/jats:styled-content> and for GPA<\/jats:styled-content> versus MPA<\/jats:styled-content>. Differences in these circulating immune mediators are more strongly associated with ANCA<\/jats:styled-content> specificity than with clinical diagnosis, suggesting that heterogeneity in the AAV<\/jats:styled-content> subtypes extends beyond clinical phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40471","type":"journal-article","created":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T06:51:01Z","timestamp":1524639061000},"page":"1114-1121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Brief Report: Circulating Cytokine Profiles and Antineutrophil Cytoplasmic Antibody Specificity in Patients With Antineutrophil Cytoplasmic Antibody\u2013Associated Vasculitis"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7831-921X","authenticated-orcid":false,"given":"Alvise","family":"Berti","sequence":"first","affiliation":[{"name":"Mayo Clinic College of Medicine and Science, Rochester, Minnesota San Raffaele University, Milan, Italy and Santa Chiara Hospital Trento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roscoe","family":"Warner","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent","family":"Johnson","sequence":"additional","affiliation":[{"name":"University of Michigan Medical School Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divi","family":"Cornec","sequence":"additional","affiliation":[{"name":"Mayo Clinic College of Medicine and Science, Rochester, Minnesota and Universit\u00e9 de Bretagne Occidentale, CHU de Brest Brest France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrell","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Mayo Clinic College of Medicine and Science Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Kabat","sequence":"additional","affiliation":[{"name":"Mayo Clinic College of Medicine and Science Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Langford","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanado C.","family":"Fervenza","sequence":"additional","affiliation":[{"name":"Mayo Clinic College of Medicine and Science Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cees G. 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