Validation of a novel multi-biomarker test to assess rheumatoid arthritis disease activity.

Curtis JR, van der Helm-van Mil AH, Knevel R, Huizinga TW, Haney DJ, Shen Y, Ramanujan S, Cavet G, Centola M, Hesterberg LK, Chernoff D, Ford K, Shadick NA, Hamburger M, Fleischmann R, Keystone E, Weinblatt ME.
Journal   Arthritis Care Res.
Species  
Analytes Measured   CRP , EGF , IL-6 , Leptin , MMP-1 , MMP-3 total , Resistin , SAA , TNF-RI , VCAM-1 , Flt-1 VEGFR1
Matrix Tested   Serum
Year   2012
Volume  
Page Numbers  
Application   Cytokines and Chemokines
Abstract
OBJECTIVE.: Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision-making. We validated a recently-developed multi-biomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts. METHODS.: Serum samples were obtained from the InFoRM, BRASS, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a pre-specified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson correlations and area under the receiver operator characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6-12 weeks after initiation of anti-TNF or methotrexate treatment were evaluated by AUROC. RESULTS.: The MBDA score was significantly associated with DAS28-CRP in both seropositive (AUROC=0.77; P<0.001) and seronegative patients (AUROC=0.70; P<0.001). In subgroups based on age, sex, body-mass index, and treatment, the MBDA score was associated with DAS28-CRP (P<0.05) in all seropositive and most seronegative subgroups. Changes in MBDA score at 6-12 weeks could discriminate both ACR50 responses (P=0.03) and DAS28-CRP improvement (P=0.002). Changes in MBDA score at 2 weeks were also associated with subsequent DAS28-CRP response (P=0.02). CONCLUSION.: Our findings establish the criterion and discriminant validity of a novel multi-biomarker test as an objective measure of RA disease activity to aid in the management of RA patients.

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VCAM-1
V-PLEX Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Plus Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX NHP IL-6 Kit
IL-6 | Non-human primate
Singleplex
V-PLEX Plus NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Plus NHP IL-6 Kit
IL-6 | Non-human primate
Singleplex
V-PLEX Plus Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Human CRP Kit
CRP | Human
Singleplex
V-PLEX Human Flt-1 Kit
VEGFR-1/Flt-1 | Human
Singleplex
V-PLEX Human SAA Kit
SAA | Human
Singleplex
V-PLEX Human VCAM-1 Kit
VCAM-1 | Human
Singleplex
V-PLEX Plus Human CRP Kit
CRP | Human
Singleplex
V-PLEX Plus Human Flt-1 Kit
VEGFR-1/Flt-1 | Human
Singleplex
V-PLEX Plus Human SAA Kit
SAA | Human
Singleplex
V-PLEX Plus Human VCAM-1 Kit
VCAM-1 | Human
Singleplex
V-PLEX Plus Vascular Injury Panel 2 Human Kit
CRP, ICAM-1, SAA, VCAM-1 | Human
Multiplex
V-PLEX Vascular Injury Panel 2 Human Kit
CRP, ICAM-1, SAA, VCAM-1 | Human
Multiplex
Vascular Injury Control Pack 1
CRP, ICAM-1, SAA, VCAM-1
Human IL-6 Antibody Bulk Product
IL-6
Mouse IL-6 Antibody
IL-6
Rat IL-6 Antibody
IL-6
V-PLEX Human Cytokine 30-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Human IL-6 Kit
IL-6 | Human
Singleplex
V-PLEX Human Proinflammatory Panel I (4-Plex)
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
V-PLEX Human Proinflammatory Panel II (4-Plex)
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
V-PLEX Mouse IL-6 Kit
IL-6 | Mouse
Singleplex
V-PLEX Plus Human Cytokine 30-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Plus Human IL-6 Kit
IL-6 | Human
Singleplex
V-PLEX Plus Human Proinflam. Panel I (4-Plex)
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
V-PLEX Plus Human Proinflam. Panel II (4-Plex)
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
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