PMID- 29693324 OWN - NLM STAT- MEDLINE DCOM- 20190722 LR - 20191028 IS - 2326-5205 (Electronic) IS - 2326-5191 (Print) IS - 2326-5191 (Linking) VI - 70 IP - 7 DP - 2018 Jul TI - Brief Report: Circulating Cytokine Profiles and Antineutrophil Cytoplasmic Antibody Specificity in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. PG - 1114-1121 LID - 10.1002/art.40471 [doi] AB - OBJECTIVE: To evaluate circulating cytokine profiles in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), classified by antineutrophil cytoplasmic antibody (ANCA) specificity (proteinase 3 ANCA [PR3-ANCA] versus myeloperoxidase ANCA [MPO-ANCA]) or by clinical diagnosis (granulomatosis with polyangiitis [GPA] versus microscopic polyangiitis [MPA]). METHODS: A panel of 29 cytokines was tested in 186 patients with active AAV at inclusion into the Rituximab in AAV 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 specificity and clinical diagnosis as explanatory variables of interest. RESULTS: Levels of 9 circulating cytokines (interleukin-6 [IL-6], granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-15, IL-18, CXCL8/IL-8, CCL-17/thymus and activation-regulated chemokine [TARC], IL-18 binding protein [IL-18 BP], soluble IL-2 receptor alpha [sIL-2Ralpha], and nerve growth factor beta [NGFbeta]) were significantly higher in PR3-AAV than MPO-AAV, 4 cytokines (sIL6R, soluble tumor necrosis factor receptor type II [sTNFRII], neutrophil gelatinase-associated lipocalin [NGAL], and soluble intercellular adhesion molecule 1 [sICAM-1]) were higher in MPO-AAV than in PR3-AAV, 6 cytokines (IL-6, GM-CSF, IL-15, IL-18, sIL-2Ralpha, and NGFbeta) were higher in GPA than in MPA, and 3 cytokines (osteopontin, sTNFRII, and NGAL) were higher in MPA than in GPA (all P < 0.05). For nearly all cytokines, the difference between PR3-AAV and MPO-AAV was larger than that between GPA and MPA. The multivariate analysis showed that 8 cytokines (IL-15, IL-8, IL-18 BP, NGF-beta, sICAM-1, TARC, osteopontin, and kidney injury molecule 1 (P < 0.05) distinguished patients with AAV better (lower P values and larger effect sizes) when grouped by ANCA specificity than by clinical diagnosis. CONCLUSION: Distinct cytokine profiles were identified for PR3-AAV versus MPO-AAV and for GPA versus MPA. Differences in these circulating immune mediators are more strongly associated with ANCA specificity than with clinical diagnosis, suggesting that heterogeneity in the AAV subtypes extends beyond clinical phenotypes. CI - (c) 2018, American College of Rheumatology. FAU - Berti, Alvise AU - Berti A AUID- ORCID: 0000-0002-7831-921X AD - Mayo Clinic College of Medicine and Science, Rochester, Minnesota, San Raffaele University, Milan, Italy, and Santa Chiara Hospital, Trento, Italy. FAU - Warner, Roscoe AU - Warner R AD - University of Michigan Medical School, Ann Arbor. FAU - Johnson, Kent AU - Johnson K AD - University of Michigan Medical School, Ann Arbor. FAU - Cornec, Divi AU - Cornec D AD - Mayo Clinic College of Medicine and Science, Rochester, Minnesota, and Universite de Bretagne Occidentale, CHU de Brest, Brest, France. FAU - Schroeder, Darrell AU - Schroeder D AD - Mayo Clinic College of Medicine and Science, Rochester, Minnesota. FAU - Kabat, Brian AU - Kabat B AD - Mayo Clinic College of Medicine and Science, Rochester, Minnesota. FAU - Langford, Carol A AU - Langford CA AD - Cleveland Clinic, Cleveland, Ohio. FAU - Hoffman, Gary S AU - Hoffman GS AD - Cleveland Clinic, Cleveland, Ohio. FAU - Fervenza, Fernanado C AU - Fervenza FC AD - Mayo Clinic College of Medicine and Science, Rochester, Minnesota. FAU - Kallenberg, Cees G M AU - Kallenberg CGM AD - University Medical Center Groningen, Groningen, The Netherlands. FAU - Seo, Philip AU - Seo P AD - Johns Hopkins University, Baltimore, Maryland. FAU - Spiera, Robert AU - Spiera R AD - Hospital for Special Surgery, New York, New York. FAU - St Clair, E William AU - St Clair EW AD - Duke University Medical Center, Durham, North Carolina. FAU - Brunetta, Paul AU - Brunetta P AD - Genentech, South San Francisco, California. FAU - Stone, John H AU - Stone JH AD - Massachusetts General Hospital, Boston. FAU - Merkel, Peter A AU - Merkel PA AD - University of Pennsylvania, Philadelphia. FAU - Specks, Ulrich AU - Specks U AD - Mayo Clinic College of Medicine and Science, Rochester, Minnesota. FAU - Monach, Paul A AU - Monach PA AD - Boston University and VA Boston Healthcare System, Boston, Massachusetts. CN - RAVE-ITN Research Group LA - eng GR - N01 AI015416/AI/NIAID NIH HHS/United States GR - UL1 RR025005/RR/NCRR NIH HHS/United States GR - RC1 AR058303/AR/NIAMS NIH HHS/United States GR - N01 AI015416/AI/NIAID NIH HHS/United States GR - K23 AR052820/AR/NIAMS NIH HHS/United States GR - M01 RR000533/RR/NCRR NIH HHS/United States GR - UL1 RR025771/RR/NCRR NIH HHS/United States GR - K24 AR002224/AR/NIAMS NIH HHS/United States GR - P60 AR047785/AR/NIAMS NIH HHS/United States GR - U54 RR019497/RR/NCRR NIH HHS/United States GR - U54 NS064808/NS/NINDS NIH HHS/United States GR - K24 AR049185/AR/NIAMS NIH HHS/United States GR - UL1 RR024150/RR/NCRR NIH HHS/United States GR - U54 AR057319/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180507 PL - United States TA - Arthritis Rheumatol JT - Arthritis & rheumatology (Hoboken, N.J.) JID - 101623795 RN - 0 (Antibodies, Antineutrophil Cytoplasmic) RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - EC 1.11.1.7 (Peroxidase) RN - EC 3.4.21.76 (Myeloblastin) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/*blood/immunology MH - Antibodies, Antineutrophil Cytoplasmic/*blood/immunology MH - Biomarkers/blood MH - Cytokines/*blood/immunology MH - Double-Blind Method MH - Female MH - Granulomatosis with Polyangiitis/blood/immunology MH - Humans MH - Male MH - Microscopic Polyangiitis/blood/immunology MH - Middle Aged MH - Myeloblastin/immunology MH - Peroxidase/immunology MH - Prospective Studies MH - Randomized Controlled Trials as Topic MH - Sensitivity and Specificity MH - Young Adult PMC - PMC6093207 MID - NIHMS946892 EDAT- 2018/04/26 06:00 MHDA- 2019/07/23 06:00 PMCR- 2019/07/01 CRDT- 2018/04/26 06:00 PHST- 2017/10/06 00:00 [received] PHST- 2018/02/22 00:00 [accepted] PHST- 2018/04/26 06:00 [pubmed] PHST- 2019/07/23 06:00 [medline] PHST- 2018/04/26 06:00 [entrez] PHST- 2019/07/01 00:00 [pmc-release] AID - 10.1002/art.40471 [doi] PST - ppublish SO - Arthritis Rheumatol. 2018 Jul;70(7):1114-1121. doi: 10.1002/art.40471. Epub 2018 May 7.