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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U-PLEX Human IL-4 384-Well Assay IL-4 \| Human Singleplex
U-PLEX Human MCP-1 384-Well Assay MCP-1 \| Human Singleplex
U-PLEX Custom Metabolic Group 1 (human) 384-well 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 Biomarker Group 1 (human) 384-well 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
S-PLEX Proinflammatory Panel 1 (human) Kit IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A, TNF-α \| Human Multiplex
U-PLEX Macrophage M2 Combo 1 (mouse) IL-4, IL-10, IL-13, MDC, TARC \| Mouse Multiplex
S-PLEX Human IL-13 Kit IL-13 \| Human Singleplex
S-PLEX NHP IL-2 Kit IL-2 \| Non-human primate Singleplex
S-PLEX NHP IL-6 Kit IL-6 \| Non-human primate Singleplex
S-PLEX NHP IL-5 Kit IL-5 \| Non-human primate Singleplex
S-PLEX NHP G-CSF Kit G-CSF \| Non-human primate Singleplex
S-PLEX Human IL-6 Kit IL-6 \| Human Singleplex
S-PLEX Human IL-10 Kit IL-10 \| Human Singleplex
S-PLEX Human IL-4 Kit IL-4 \| Human Singleplex
S-PLEX Human IL-2 Kit IL-2 \| Human Singleplex
S-PLEX Human IL-5 Kit IL-5 \| Human Singleplex
S-PLEX Human G-CSF Kit G-CSF \| Human Singleplex
S-PLEX Human IL-17A Kit IL-17A \| Human Singleplex
S-PLEX Human GM-CSF Kit GM-CSF \| Human Singleplex
U-PLEX CAR-T Cell Combo 1 (human) GM-CSF, Granzyme A, Granzyme B, IFN-γ, IL-2, TNF-α \| Human 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 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 TH17 Combo 3 (mouse) IL-16, IL-17A, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-31, MIP-3α \| Mouse Multiplex
V-PLEX Viral Panel 3 NHP Kit IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Viral Panel 3 Human Kit IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 3 NHP Kit IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Plus Viral Panel 3 Human Kit IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α \| Human Multiplex
U-PLEX Viral Combo 1 (NHP) G-CSF, GM-CSF, IFN-α2a, IFN-γ, IL-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IP-10, MCP-1, MIP-1α, TNF-α, VEGF-A \| Non-human primate Multiplex
U-PLEX Viral Combo 1 (human) G-CSF, GM-CSF, IFN-α2a, IFN-β, IFN-γ, IL-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IP-10, MCP-1, MIP-1α, TNF-α, VEGF-A \| Human Multiplex
V-PLEX Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex
V-PLEX Viral Panel 1 NHP Kit IL-1β, IL-6, IL-8 \| Non-human primate Multiplex
V-PLEX Viral Panel 1 Human Kit IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Plus Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 1 NHP Kit IL-1β, IL-6, IL-8 \| Non-human primate Multiplex
V-PLEX Plus Viral Panel 1 Human Kit IL-1β, IL-6, IL-8, TNF-α \| Human Multiplex
U-PLEX NHP IL-2 Assay IL-2 \| Non-human primate Singleplex
U-PLEX NHP IL-8 Assay IL-8 \| Non-human primate Singleplex
U-PLEX NHP IL-6 Assay IL-6 \| Non-human primate Singleplex
U-PLEX NHP IL-10 Assay IL-10 \| Non-human primate Singleplex
U-PLEX NHP GM-CSF Assay GM-CSF \| Non-human primate Singleplex
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A signature of aberrant immune responsiveness identifies myocardial dysfunction in rheumatoid arthritis.

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