PMID- 22975753 OWN - NLM STAT- MEDLINE DCOM- 20130919 LR - 20220409 IS - 1468-2060 (Electronic) IS - 0003-4967 (Print) IS - 0003-4967 (Linking) VI - 72 IP - 8 DP - 2013 Aug TI - Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. PG - 1342-50 LID - 10.1136/annrheumdis-2012-201981 [doi] AB - OBJECTIVE: To identify circulating proteins that distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner complementary to markers of systemic inflammation. METHODS: Twenty-eight serum proteins representing diverse aspects of the biology of AAV were measured before and 6 months after treatment in a large clinical trial of AAV. Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were available for comparison. The primary outcome was the ability of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for Wegener's granulomatosis (BVAS/WG)>/=3 at screening) from remission (BVAS/WG=0 at month 6), using areas under receiver operating characteristic (ROC) curve (AUC). RESULTS: All subjects had severe active vasculitis (median BVAS/WG=8) at screening. In the 137 subjects in remission at month 6, 24 of the 28 markers showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) best discriminated active AAV from remission (AUC>0.8) and from healthy controls (AUC>0.9). Correlations among these markers and with ESR or CRP were low. CONCLUSIONS: Many markers are elevated in severe active AAV and decline with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from remission better than the other markers studied, including ESR and CRP. These proteins are particularly promising candidates for future studies to address unmet needs in the assessment of patients with AAV. FAU - Monach, Paul A AU - Monach PA AD - Vasculitis Center, Section of Rheumatology, and the Clinical Epidemiology Unit, Boston University School of Medicine, Boston, MA, USA. FAU - Warner, Roscoe L AU - Warner RL FAU - Tomasson, Gunnar AU - Tomasson G FAU - Specks, Ulrich AU - Specks U FAU - Stone, John H AU - Stone JH FAU - Ding, Linna AU - Ding L FAU - Fervenza, Fernando C AU - Fervenza FC FAU - Fessler, Barri J AU - Fessler BJ FAU - Hoffman, Gary S AU - Hoffman GS FAU - Ikle, David AU - Ikle D FAU - Kallenberg, Cees G M AU - Kallenberg CG FAU - Krischer, Jeffrey AU - Krischer J FAU - Langford, Carol A AU - Langford CA FAU - Mueller, Mark AU - Mueller M FAU - Seo, Philip AU - Seo P FAU - St Clair, E William AU - St Clair EW FAU - Spiera, Robert AU - Spiera R FAU - Tchao, Nadia AU - Tchao N FAU - Ytterberg, Steven R AU - Ytterberg SR FAU - Johnson, Kent J AU - Johnson KJ FAU - Merkel, Peter A AU - Merkel PA LA - eng GR - RR024150-01/RR/NCRR NIH HHS/United States GR - K24 AR02224/AR/NIAMS NIH HHS/United States GR - UL1 RR025005/RR/NCRR 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 - P60 AR047785/AR/NIAMS NIH HHS/United States GR - U54 RR019497/RR/NCRR NIH HHS/United States GR - M01 RR001066/RR/NCRR NIH HHS/United States GR - UL1 TR000439/TR/NCATS NIH HHS/United States GR - UL1 RR024150/RR/NCRR NIH HHS/United States GR - U54AR057319/AR/NIAMS NIH HHS/United States GR - RC1 AR058303/AR/NIAMS NIH HHS/United States GR - N01 AI015416/AI/NIAID NIH HHS/United States GR - K24 AR002224/AR/NIAMS NIH HHS/United States GR - NS064808/NS/NINDS NIH HHS/United States GR - RR 025771/RR/NCRR NIH HHS/United States GR - U54 NS064808/NS/NINDS NIH HHS/United States GR - M01 RR00533/RR/NCRR NIH HHS/United States GR - K24 AR049185/AR/NIAMS NIH HHS/United States GR - RR025005/RR/NCRR NIH HHS/United States GR - U54 AR057319/AR/NIAMS NIH HHS/United States GR - P60AR047785/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120912 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Antibodies, Monoclonal, Murine-Derived) RN - 0 (Biomarkers) RN - 0 (CXCL13 protein, human) RN - 0 (Chemokine CXCL13) RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (Immunologic Factors) RN - 0 (Proteins) RN - 0 (TIMP1 protein, human) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 4F4X42SYQ6 (Rituximab) RN - 9007-41-4 (C-Reactive Protein) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Adult MH - Aged MH - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/*blood/drug therapy/*pathology MH - Antibodies, Monoclonal, Murine-Derived/therapeutic use MH - Biomarkers/blood MH - Blood Sedimentation MH - C-Reactive Protein/analysis MH - Chemokine CXCL13/blood MH - Chemokines/blood MH - Cytokines/blood MH - Double-Blind Method MH - Female MH - Health Status MH - Humans MH - Immunologic Factors/therapeutic use MH - Male MH - Matrix Metalloproteinase 3/blood MH - Middle Aged MH - Proteins/*metabolism MH - ROC Curve MH - Remission Induction MH - Rituximab MH - Severity of Illness Index MH - Tissue Inhibitor of Metalloproteinase-1/blood PMC - PMC4982463 MID - NIHMS801401 OTO - NOTNLM OT - Autoimmune Diseases OT - Chemokines OT - Cytokines COIS- Competing interests None. EDAT- 2012/09/15 06:00 MHDA- 2013/09/21 06:00 PMCR- 2016/08/12 CRDT- 2012/09/15 06:00 PHST- 2012/09/15 06:00 [entrez] PHST- 2012/09/15 06:00 [pubmed] PHST- 2013/09/21 06:00 [medline] PHST- 2016/08/12 00:00 [pmc-release] AID - annrheumdis-2012-201981 [pii] AID - 10.1136/annrheumdis-2012-201981 [doi] PST - ppublish SO - Ann Rheum Dis. 2013 Aug;72(8):1342-50. doi: 10.1136/annrheumdis-2012-201981. Epub 2012 Sep 12.