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

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.

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Identifiers

ORCID for Helena L. Fisk: orcid.org/0000-0002-9534-3246

ORCID for Philip C. Calder: orcid.org/0000-0002-6038-710X

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