TY - JOUR
T1 - Evaluation of Potential Serum Biomarkers of Disease Activity in Diverse Forms of Vasculitis
AU - Rodriguez-Pla, Alicia
AU - Warner, Roscoe L.
AU - Cuthbertson, David
AU - Carette, Simon
AU - Khalidi, Nader A.
AU - Koening, Curry L.
AU - Langford, Carol A.
AU - McAlear, Carol A.
AU - Moreland, Larry W.
AU - Pagnoux, Christian
AU - Seo, Philip
AU - Specks, Ulrich
AU - Sreih, Antoine G.
AU - Ytterberg, Steven R.
AU - Johnson, Kent J.
AU - Merkel, Peter A.
AU - Monach, Paul A.
N1 - Funding Information:
From Boston University, Boston, Massachusetts; University of Arizona, Tucson, Arizona; University of Michigan, Ann Arbor, Michigan; University of South Florida, Tampa, Florida, USA; Mount Sinai Hospital, Toronto; McMaster University, Hamilton, Ontario, Canada; University of Utah, Salt Lake City, Utah; Cleveland Clinic, Cleveland, Ohio; University of Pennsylvania, Philadelphia; University of Pittsburgh, Pittsburgh, Pennsylvania; Johns Hopkins University, Baltimore, Maryland; Mayo Clinic, Rochester, Minnesota; VA Boston Healthcare System, Boston, Massachusetts, USA. This work was sponsored by the Vasculitis Clinical Research Consortium (VCRC). The consortium is part of the Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Science (NCATS). The VCRC is funded through collaboration between NCATS and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319), and has received funding from the National Center for Research Resources (U54 RR019497). Additional funding for this project included RC1 AR 058303 and P60 AR047785.
Publisher Copyright:
©2020. All rights reserved.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Objective. We evaluated potential circulating biomarkers of disease activity in giant cell arteritis (GCA), Takayasu arteritis (TA), polyarteritis nodosa (PAN), and eosinophilic granulomatosis with polyangiitis (EGPA). Methods. A panel of 22 serum proteins was tested in patients enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies of GCA, TA, PAN, or EGPA. Mixed models were used for most analyses. A J48 classification tree method was used to find the most relevant markers to differentiate between active and inactive GCA. Results. Tests were done on 418 samples from 152 patients (60 GCA, 29 TA, 26 PAN, 37 EGPA), during both active vasculitis and remission. In GCA, these showed significant (p < 0.05) differences between disease states: B cell-attracting chemokine 1 (BCA)-1/CXC motif ligand 13 (CXCL13), erythrocyte sedimentation rate (ESR), interferon-γ-induced protein 10/CXC motif chemokine 10, soluble interleukin 2 receptor α (sIL-2Rα), and tissue inhibitor of metalloproteinase-1 (TIMP-1). In EGPA, these showed significant increases during active disease: granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF, interleukin (IL)-6, IL-15, and sIL-2Rα. BCA-1/CXCL13 also showed such increases, but only after adjustment for treatment. In PAN, ESR and matrix metalloprotease (MMP)-3 showed significant differences between disease states. Differences in biomarker levels between diseases were significant for 11 markers and were more striking (all p < 0.01) than differences related to disease activity. A combination of lower values of TIMP-1, IL-6, interferon-γ, and MMP-3 correctly classified 87% of samples with inactive GCA. Conclusion. We identified novel biomarkers of disease activity in GCA and EGPA. Differences of biomarker levels between diseases, independent of disease activity, were more apparent than differences related to disease activity. Further studies are needed to determine whether these serum proteins have potential for clinical use in distinguishing active disease from remission or in predicting longer-term outcomes.
AB - Objective. We evaluated potential circulating biomarkers of disease activity in giant cell arteritis (GCA), Takayasu arteritis (TA), polyarteritis nodosa (PAN), and eosinophilic granulomatosis with polyangiitis (EGPA). Methods. A panel of 22 serum proteins was tested in patients enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies of GCA, TA, PAN, or EGPA. Mixed models were used for most analyses. A J48 classification tree method was used to find the most relevant markers to differentiate between active and inactive GCA. Results. Tests were done on 418 samples from 152 patients (60 GCA, 29 TA, 26 PAN, 37 EGPA), during both active vasculitis and remission. In GCA, these showed significant (p < 0.05) differences between disease states: B cell-attracting chemokine 1 (BCA)-1/CXC motif ligand 13 (CXCL13), erythrocyte sedimentation rate (ESR), interferon-γ-induced protein 10/CXC motif chemokine 10, soluble interleukin 2 receptor α (sIL-2Rα), and tissue inhibitor of metalloproteinase-1 (TIMP-1). In EGPA, these showed significant increases during active disease: granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF, interleukin (IL)-6, IL-15, and sIL-2Rα. BCA-1/CXCL13 also showed such increases, but only after adjustment for treatment. In PAN, ESR and matrix metalloprotease (MMP)-3 showed significant differences between disease states. Differences in biomarker levels between diseases were significant for 11 markers and were more striking (all p < 0.01) than differences related to disease activity. A combination of lower values of TIMP-1, IL-6, interferon-γ, and MMP-3 correctly classified 87% of samples with inactive GCA. Conclusion. We identified novel biomarkers of disease activity in GCA and EGPA. Differences of biomarker levels between diseases, independent of disease activity, were more apparent than differences related to disease activity. Further studies are needed to determine whether these serum proteins have potential for clinical use in distinguishing active disease from remission or in predicting longer-term outcomes.
KW - Vasculitis biomarkers takayasu arteritis eosinophilic granulomatosis with polyangiitis polyarteritis nodosa
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U2 - 10.3899/jrheum.190093
DO - 10.3899/jrheum.190093
M3 - Article
C2 - 31474593
AN - SCOPUS:85077690716
SN - 0315-162X
VL - 47
SP - 1001
EP - 1010
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 7
ER -