Abstract
Objective
To determine whether levels of plasma n-3 PUFAs are associated with response to anti-TNF agents in 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 three months of anti-TNF treatment in 22 patients with established RA, and fatty acid composition of the phosphatidylcholine (PC) component measured. CD4+CD25- T cells and monocytes were purified from the blood of healthy donors and co-cultured in the presence of anti-CD3, with or without etanercept, EPA or the control fatty acid, linoleic acid (LA). Expression of IL-17 and IFNγ was measured by intracellular staining and flow cytometry.
Results
Plasma PC EPA levels, and the EPA/arachidonic acid ratio, correlated inversely with change in DAS28 scores 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 EULAR response (P=0.02). An increase in Th17 cells post-therapy has been associated with non-response to anti-TNF. Etanercept 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 etanercept on Th17 cells in vitro. EPA supplementation might be a simple way to improve anti-TNF outcomes in RA patients by suppressing Th17 frequencies.
To determine whether levels of plasma n-3 PUFAs are associated with response to anti-TNF agents in 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 three months of anti-TNF treatment in 22 patients with established RA, and fatty acid composition of the phosphatidylcholine (PC) component measured. CD4+CD25- T cells and monocytes were purified from the blood of healthy donors and co-cultured in the presence of anti-CD3, with or without etanercept, EPA or the control fatty acid, linoleic acid (LA). Expression of IL-17 and IFNγ was measured by intracellular staining and flow cytometry.
Results
Plasma PC EPA levels, and the EPA/arachidonic acid ratio, correlated inversely with change in DAS28 scores 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 EULAR response (P=0.02). An increase in Th17 cells post-therapy has been associated with non-response to anti-TNF. Etanercept 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 etanercept on Th17 cells in vitro. EPA supplementation might be a simple way to improve anti-TNF outcomes in RA patients by suppressing Th17 frequencies.
Original language | English |
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Pages (from-to) | 748-756 |
Number of pages | 9 |
Journal | The Journal of Rheumatology |
Volume | 44 |
Issue number | 6 |
DOIs | |
Publication status | Published - 1 Jun 2017 |
Keywords
- Rheumatoid arthritis
- anti-TNF
- polyunsaturated fatty acids
- eicosapentaenoic acid
- omega-3
- Th17