Plasma levels of eicosapentaenoic acid are associated with anti-TNF responsiveness in rheumatoid arthritis and inhibit the etanercept-driven rise in Th17 cell differentiation in vitro

Jeffery, L., Fisk, H. L., Calder, P. C., Filer, A., Raza, K., Buckley, C. D., McInnes, I. , Taylor, P. C. and Fisher, B. A. (2017) Plasma levels of eicosapentaenoic acid are associated with anti-TNF responsiveness in rheumatoid arthritis and inhibit the etanercept-driven rise in Th17 cell differentiation in vitro. Journal of Rheumatology, 44(6), pp. 748-756. (doi:10.3899/jrheum.161068) (PMID:28202745)

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Abstract

Objective: To determine whether levels of plasma n-3 polyunsaturated fatty acids are associated with response to antitumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA), and whether this putative effect may have its basis in altering anti-TNF–driven Th17 cell differentiation. Methods: Plasma was collected at baseline and after 3 months of anti-TNF treatment in 22 patients with established RA, and fatty acid composition of the phosphatidylcholine (PC) component was measured. CD4+CD25– T cells and monocytes were purified from the blood of healthy donors and cocultured in the presence of anti-CD3, with or without etanercept (ETN), eicosapentaenoic acid (EPA), or the control fatty acid, linoleic acid (LA). Expression of interleukin 17 and interferon-γ was measured by intracellular staining and flow cytometry. Results: Plasma PC EPA levels and the EPA/arachidonic acid ratio correlated inversely with change in the Disease Activity Score at 28 joints (DAS28) at 3 months (–0.51, p = 0.007 and –0.48, p = 0.01, respectively), indicating that higher plasma EPA was associated with a greater reduction in DAS28. Plasma PC EPA was positively associated with European League Against Rheumatism response (p = 0.02). An increase in Th17 cells post-therapy has been associated with nonresponse to anti-TNF. ETN increased Th17 frequencies in vitro. Physiological concentrations of EPA, but not LA, prevented this. Conclusion: EPA status was associated with clinical improvements to anti-TNF therapy in vivo and prevented the effect of ETN on Th17 cells in vitro. EPA supplementation might be a simple way to improve anti-TNF outcomes in patients with RA by suppressing Th17 frequencies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Filer, Dr Andrew
Authors: Jeffery, L., Fisk, H. L., Calder, P. C., Filer, A., Raza, K., Buckley, C. D., McInnes, I., Taylor, P. C., and Fisher, B. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Rheumatology
Publisher:Journal of Rheumatology
ISSN:0315-162X
ISSN (Online):1499-2752
Published Online:15 February 2017

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