Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity.

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Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity.

Davis JM 3rd, Knutson KL, Strausbauch MA, Green AB, Crowson CS, Therneau TM, Matteson EL, Gabriel SE.

Journal		Arthritis Res Ther.
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		Cell culture supernatants

Year		2013
Volume		15
Page Numbers		199
Application		Cytokines and Chemokines

Abstract

INTRODUCTION: It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA.

METHODS: A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2.

RESULTS: A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P = 0.32), suggesting this response was related to CMV exposure.

CONCLUSIONS: A profile of T-cell immunity associated with CMV exposure influences the clinical response to DMARD therapy in patients with early RA. Because CMV latency is associated with greater joint destruction, our findings suggest that changes in T-cell immunity mediated by viral persistence may affect treatment response and possibly long-term outcomes of RA.

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U-PLEX Viral Combo 1 (hu) 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 Human IL-17A Assay IL-17A \| Human Singleplex
U-PLEX Human IL-13 Assay IL-13 \| Human Singleplex
U-PLEX Human IL-10 Assay IL-10 \| Human Singleplex
U-PLEX Human GM-CSF Assay GM-CSF \| Human Singleplex
U-PLEX Human G-CSF Assay G-CSF \| Human Singleplex
U-PLEX Human MCP-1 Assay MCP-1 \| Human Singleplex
U-PLEX Human IL-8 Assay IL-8 \| Human Singleplex
U-PLEX Human IL-7 Assay IL-7 \| Human Singleplex
U-PLEX Human IL-6 Assay IL-6 \| Human Singleplex
U-PLEX Human IL-5 Assay IL-5 \| Human Singleplex
U-PLEX Human IL-4 Assay IL-4 \| Human Singleplex
U-PLEX Human IL-2 Assay IL-2 \| Human Singleplex
U-PLEX NHP IL-5 Assay IL-5 \| Non-human primate Singleplex
U-PLEX NHP IL-4 Assay IL-4 \| Non-human primate Singleplex
U-PLEX NHP IL-2 Assay IL-2 \| Non-human primate Singleplex
U-PLEX NHP IL-17A Assay IL-17A \| Non-human primate Singleplex
U-PLEX NHP IL-13 Assay IL-13 \| 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
U-PLEX NHP G-CSF Assay G-CSF \| Non-human primate Singleplex
U-PLEX NHP MCP-1 Assay MCP-1 \| Non-human primate Singleplex
U-PLEX NHP IL-8 Assay IL-8 \| Non-human primate Singleplex
U-PLEX NHP IL-7 Assay IL-7 \| Non-human primate Singleplex
U-PLEX NHP IL-6 Assay IL-6 \| Non-human primate Singleplex
U-PLEX Mouse MCP-1 Assay MCP-1 \| Mouse Singleplex
U-PLEX Mouse IL-17A Assay IL-17A \| Mouse Singleplex
U-PLEX Mouse IL-13 Assay IL-13 \| Mouse Singleplex
U-PLEX Mouse IL-10 Assay IL-10 \| Mouse Singleplex
U-PLEX Mouse IL-6 Assay IL-6 \| Mouse Singleplex
U-PLEX Mouse IL-5 Assay IL-5 \| Mouse Singleplex
U-PLEX Mouse IL-4 Assay IL-4 \| Mouse Singleplex
U-PLEX Mouse IL-2 Assay IL-2 \| Mouse Singleplex
U-PLEX Mouse GM-CSF Assay GM-CSF \| Mouse Singleplex
Mouse IL-12 (total) Tissue Culture Kit IL-12 (total) \| Mouse Singleplex
Mouse IL-12 (total) Ultra-Sensitive Kit IL-12 (total) \| Mouse Singleplex
R-PLEX Rat GM-CSF Assay GM-CSF \| Rat Singleplex
R-PLEX Rat IL-2 Assay IL-2 \| Rat Singleplex
R-PLEX Rat IL-4 Assay IL-4 \| Rat Singleplex
R-PLEX Rat IL-5 Assay IL-5 \| Rat Singleplex
R-PLEX Rat IL-6 Assay IL-6 \| Rat Singleplex
R-PLEX Rat IL-10 Assay IL-10 \| Rat Singleplex
R-PLEX Rat IL-13 Assay IL-13 \| Rat Singleplex
R-PLEX Rat MCP-1 Assay MCP-1 \| Rat Singleplex
U-PLEX Metabolic Group 1 (ms) Assay Mouse Multiplex
U-PLEX Custom Metabolic Group 1 (ms) Assay Mouse Multiplex
U-PLEX Adipokine Combo 1 (ms) BDNF, IL-1β, IL-6, IL-10, Insulin, Leptin, MCP-1, TNF-α \| Mouse Multiplex
U-PLEX Chemokine Combo 1 (ms) IP-10, KC/GRO, MCP-1, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α \| Mouse Multiplex
U-PLEX Metabolic Hormones Combo 1 (ms) C-Peptide, Ghrelin (active), GLP-1 (active), Glucagon, IL-6, Insulin, Leptin, MCP-1, PYY (total), TNF-α \| Mouse Multiplex
U-PLEX Metabolic Group 1 (ms) 58-Plex 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 Biomarker Group 1 (ms) 50-Plex 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 Metabolic Group 1 (hu) 87-Plex 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 (hu) 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 Metabolic Group 1 (hu) 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 Adipokine Combo 1 (hu) BDNF, β-NGF, IL-1β, IL-6, IL-8, IL-10, Insulin, Leptin, MCP-1, TNF-α \| Human Multiplex
R-PLEX Rat IL-5 Antibody Set IL-5 \| Rat
R-PLEX Rat IL-4 Antibody Set IL-4 \| Rat
R-PLEX Rat IL-2 Antibody Set IL-2 \| Rat
R-PLEX Rat IL-13 Antibody Set IL-13 \| Rat
R-PLEX Rat IL-10 Antibody Set IL-10 \| Rat
R-PLEX Rat IL-6 Antibody Set IL-6 \| Rat
R-PLEX Rat MCP-1 Antibody Set MCP-1 \| Rat
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Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity.

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