A signature of aberrant immune responsiveness identifies myocardial dysfunction in rheumatoid arthritis.

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A signature of aberrant immune responsiveness identifies myocardial dysfunction in rheumatoid arthritis.

Davis, J.M. 3rd, Knutson, K.L., Strausbauch, M.A., Crowson, C.S., Therneau, T.M., Wettstein, P.J., Roger, V.L., Matteson, E.L., Gabriel, S.E.

Journal		Arthritis Rheum.
Species
Analytes Measured		G-CSF , GM-CSF , IL-10 , IL-12 Total , IL-13 , IL-17A , IL-2 , IL-4 , IL-5 , IL-6 , IL-7 , IL-8 , MCP-1
Matrix Tested		Peripheral blood mononuclear cell (PBMC) culture supernatants

Year		2011
Volume		63
Page Numbers		1497-1506
Application		Cytokines and Chemokines

Abstract

OBJECTIVE: Heart failure is an important cause of death in patients with rheumatoid arthritis (RA). Evidence suggests that immune mechanisms contribute to myocardial injury and fibrosis, leading to left ventricular diastolic dysfunction (LVDD). The purpose of this study was to identify a signature of LVDD in patients with RA by analyzing the responsiveness of the innate and adaptive immune systems to stimulation ex vivo.

METHODS: RA patients (n=212) enrolled prospectively in a population-based cohort underwent echocardiography, and LV function was classified as normal, mild LVDD, or moderate-to-severe LVDD. The release of 17 cytokines by blood mononuclear cells in response to stimulation with a panel of 7 stimuli or in media alone was analyzed using multiplex immunoassays. Logistic regression models were used to test for associations between a multicytokine immune response score and LVDD, after adjusting for clinical covariates.

RESULTS: An 11-cytokine profile effectively differentiated patients with moderate-to-severe LVDD from those with normal LV function. An immune response score (range 0-100) was strongly associated with moderate-to-severe LVDD (odds ratio per 10 units 1.5 [95% confidence interval 1.2-2.1]) after adjusting for serum interleukin-6 levels, brain natriuretic peptide values, and glucocorticoid use, as well as other RA characteristics and LVDD risk factors.

CONCLUSION: The major finding of this study was that aberrant systemic immune responsiveness is associated with advanced myocardial dysfunction in patients with RA. The unique information added by the immune response score concerning the likelihood of LVDD warrants future longitudinal studies of its value in predicting future deterioration in myocardial function.

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V-PLEX Plus Human IL-6 Kit IL-6 \| Human Singleplex		NEW
V-PLEX Plus Cytokine Panel 1 NHP Kit GM-CSF, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Non-human primate Multiplex		NEW
V-PLEX Plus Cytokine Panel 1 Human Kit GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Human Multiplex		NEW
V-PLEX NHP IL-7 Kit IL-7 \| Non-human primate Singleplex		NEW
V-PLEX Human IL-7 Kit IL-7 \| Human Singleplex		NEW
V-PLEX Human IL-6 Kit IL-6 \| Human Singleplex		NEW
V-PLEX Plus Human MCP-1 Gen. B Kit MCP-1 \| Human Singleplex		NEW
V-PLEX Human MCP-1 Gen. B Kit MCP-1 \| Human Singleplex		NEW
V-PLEX NHP IL-6 Kit IL-6 \| Non-human primate Singleplex		NEW
V-PLEX Plus Human Proinflam. Panel I (4-Plex) IFN-γ, IL-1β, IL-6, TNF-α \| Human Multiplex		NEW
V-PLEX Plus Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex		NEW
V-PLEX Plus Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex		NEW
V-PLEX Plus Viral Panel 1 NHP Kit IL-1β, IL-6, IL-8 \| Non-human primate Multiplex		NEW
V-PLEX Plus Viral Panel 1 Human Kit IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex		NEW
V-PLEX Plus Proinflammatory Panel 1 Human Kit IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex		NEW
V-PLEX Plus Proinflammatory Panel 1 NHP Kit IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 \| Non-human primate Multiplex		NEW
V-PLEX Plus NHP IL-10 Kit IL-10 \| Non-human primate Singleplex		NEW
V-PLEX Plus Human IL-13 Kit IL-13 \| Human Singleplex		NEW
V-PLEX Plus Human IL-10 Kit IL-10 \| Human Singleplex		NEW
V-PLEX Plus Human IL-4 Kit IL-4 \| Human Singleplex		NEW
V-PLEX NHP IL-10 Kit IL-10 \| Non-human primate Singleplex		NEW
V-PLEX Human IL-13 Kit IL-13 \| Human Singleplex		NEW
V-PLEX Human IL-10 Kit IL-10 \| Human Singleplex		NEW
V-PLEX Human IL-4 Kit IL-4 \| Human Singleplex		NEW
V-PLEX Plus Human Proinflam. Panel II (4-Plex) IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex		NEW
V-PLEX Cytokine Panel 1 Human Kit GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Human Multiplex		NEW
V-PLEX Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex		NEW
V-PLEX Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex		NEW
V-PLEX Viral Panel 1 NHP Kit IL-1β, IL-6, IL-8 \| Non-human primate Multiplex		NEW
V-PLEX Viral Panel 1 Human Kit IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex		NEW
V-PLEX Chemokine Panel 1 (human) Gen. B Kit Eotaxin, Eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC \| Human Multiplex		NEW
V-PLEX Proinflammatory Panel 1 NHP Kit IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 \| Non-human primate Multiplex		NEW
V-PLEX Human Proinflammatory Panel II (4-Plex) IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex		NEW
V-PLEX Human Proinflammatory Panel I (4-Plex) IFN-γ, IL-1β, IL-6, TNF-α \| Human Multiplex		NEW
V-PLEX Cytokine Panel 1 NHP Kit GM-CSF, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Non-human primate Multiplex		NEW
V-PLEX Proinflammatory Panel 1 Human Kit IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex		NEW
R-PLEX Rabbit IL-6 Antibody Set IL-6 \| Rabbit		NEW
R-PLEX Rabbit IL-6 Assay IL-6 \| Rabbit Singleplex		NEW
U-PLEX Biomarker Group 1 (NHP) Assays CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17F, IL-18, IL-22, IL-23, IP-10, I-TAC, MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, VEGF-A, YKL-40 \| Non-human primate Multiplex
U-PLEX Custom Biomarker Group 1 (human) Assays CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human Multiplex
U-PLEX Custom Biomarker Group 1 (mouse) Assays 6CKine/CCL21, BAFF, BCA-1/BLC, CD40/TNFRSF5, Eotaxin, EPO, GM-CSF, IFN-α, IFN-β, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, IP-10, KC/GRO, MCP-1, MCP-5/CCL12, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α, MMP-9 (total), NGAL/LCN2, RANTES, SDF-1α, TARC, TNF-α, TNF-RI, VEGF-A \| Mouse Multiplex
U-PLEX Custom Metabolic Group 1 (human) Assays BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human Multiplex
U-PLEX Custom Metabolic Group 1 (mouse) Assays BAFF, BCA-1/BLC, BDNF, CD40/TNFRSF5, C-Peptide, Eotaxin, EPO, FGF-21, Ghrelin (active), Ghrelin (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, IFN-α, IFN-β, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, Insulin, IP-10, KC/GRO, Leptin, MCP-1, MCP-5/CCL12, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α, MMP-9 (total), PYY (total), RANTES, TARC, TNF-α, VEGF-A \| Mouse Multiplex
U-PLEX Custom Immuno-Oncology Group 1 (human) Assays 4-1BBL/TNFSF9, APRIL/TNFSF13, BAFF-R/TNFRSF13C, BCMA/TNFRSF17, BTLA, CD20, CD27, CD28, CD40/TNFRSF5, CD40L (soluble), CD80/B7-1, CD276/B7-H3, CTACK, CTLA-4, E-Cadherin, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, E-Selectin, Fas (soluble), FasL, FGF (basic), FLT3L, Fractalkine, Galectin-9, G-CSF, GITR/TNFRSF18, GITRL/TNFSF18, GM-CSF, gp130 (soluble), Granzyme A, Granzyme B, GRO-α, HAVCR1/KIM-1, HAVCR2/TIM-3, HVEM/TNFRSF14, I-309, ICOS, ICOS-L/B7-H2, IDO-1, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, LAG3, LIGHT/TNFSF14, MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIG, MIP-1α, MIP-1β, MIP-5, MMP-1, MMP-2, MMP-7, MMP-8 (total), MMP-9 (total), MMP-10 (total), Nectin-4, OX40/TNFRSF4, PD1 (epitope 1), PD1 (epitope 2), PDGF-B, PD-L1 (epitope 1), PD-L1 (epitope 2), PD-L2, Pentraxin 3, Perforin, PlGF, proMMP-8, proMMP-9, proMMP-10, P-Selectin, RAGE (soluble), RANKL/TNFSF11, RANTES, S100A12, TACI/TNFRSF13B, Tie-2, TIGIT, TLR1, TNF-α, TNF-β, TNF-RI, TNF-RII, TPO, TRAIL, TSLP, VEGF-A, VEGF-D, VEGFR-1/Flt-1, YKL-40 \| Human Multiplex
U-PLEX Alzheimer's Disease Combo 1 (human) Eotaxin, IL-1α, IL-12/IL-23p40, IL-16, IL-17A, MCP-1, MDC, MIF, SDF-1α, YKL-40 \| Human Multiplex
U-PLEX Multiple Sclerosis Combo 1 (human) CTACK, Fractalkine, GRO-α, IL-7, IL-12/IL-23p40, IP-10, MCP-1, MIP-1β, MIP-3α \| Human Multiplex
U-PLEX TBI Combo 1 (human) CD40L (soluble), Fractalkine, IFN-γ, IL-1β, IL-6, IL-18, MCP-1, RANKL/TNFSF11, TNF-α, VEGF-D \| Human Multiplex
U-PLEX Chemokine Combo (mouse) IP-10, KC/GRO, MCP-1, MIP-1α, MIP-1β, MIP-2, MIP-3α \| Mouse Multiplex
U-PLEX Chemokine Combo 1 (human) Eotaxin, Eotaxin-2, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-2, MCP-3, MCP-4, MDC, MIP-1α, MIP-1β, TARC \| Human Multiplex		NEW
U-PLEX Chemokine Combo 1 (mouse) IP-10, KC/GRO, MCP-1, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α \| Mouse Multiplex
U-PLEX Chemokine Combo 1 (NHP) Eotaxin, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC \| Non-human primate Multiplex		NEW
U-PLEX Cytokine Combo 1 (human) GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Human Multiplex		NEW
U-PLEX Cytokine Combo 1 (NHP) GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Non-human primate Multiplex		NEW
U-PLEX Macrophage M1 Combo 1 (human) IL-1β, IL-6, IL-12p70, IL-18, IL-23, IP-10, MCP-1, MIP-1α, TNF-α \| Human Multiplex
U-PLEX Macrophage M1 Combo 1 (mouse) IL-1β, IL-6, IL-12p70, IL-15, IL-23, IP-10, MCP-1, MIP-1α, TNF-α \| Mouse Multiplex
U-PLEX Macrophage M2 Combo 1 (human) Eotaxin-2, IL-4, IL-10, IL-13, M-CSF, MDC, TARC \| Human Multiplex
U-PLEX Macrophage M2 Combo 1 (mouse) IL-4, IL-10, IL-13, MDC, TARC \| Mouse Multiplex
U-PLEX Proinflam Combo 1 (human) IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex		NEW
U-PLEX Proinflam Combo 1 (mouse) IFN-γ, IL-1β, IL-2, IL-6, IL-10, IL-12p70, IL-17A, IP-10, MCP-1, TNF-α \| Mouse Multiplex
U-PLEX Proinflam Combo 1 (NHP) IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12/IL-23p40, TNF-α \| Non-human primate Multiplex		NEW
U-PLEX Proinflam Combo 2 (human) GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70 \| Human Multiplex		NEW
U-PLEX Proinflam Combo 3 (human) IFN-γ, IL-1β, IL-6, TNF-α \| Human Multiplex		NEW
U-PLEX Proinflam Combo 4 (human) IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex		NEW
U-PLEX T-Cell Combo (human) GM-CSF, IFN-γ, IL-2, IL-4, IL-9, IL-10, IL-13, IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, MIP-3α, TNF-α \| Human Multiplex
U-PLEX T-Cell Combo (mouse) GM-CSF, IFN-γ, IL-2, IL-4, IL-9, IL-10, IL-13, IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, MIP-3α, TNF-α \| Mouse Multiplex
U-PLEX T-Cell Combo (NHP) GM-CSF, IFN-γ, IL-2, IL-4, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-22, MIP-3α, TNF-α \| Non-human primate Multiplex
U-PLEX TH1/TH2 Combo (human) IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex		NEW
U-PLEX TH1/TH2 Combo (mouse) IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, KC/GRO, TNF-α \| Mouse Multiplex		NEW
U-PLEX TH1/TH2 Combo (NHP) IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, TNF-α \| Non-human primate Multiplex
U-PLEX TH17 Combo 1 (human) IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27, IL-31, IL-33 \| Human Multiplex
U-PLEX TH17 Combo 1 (mouse) IL-17A, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-31, IL-33 \| Mouse Multiplex
U-PLEX TH17 Combo 1 (NHP) IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17A, TNF-α \| Non-human primate Multiplex
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A signature of aberrant immune responsiveness identifies myocardial dysfunction in rheumatoid arthritis.

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