Background/Purpose:

The prostanoids are a family of biologically active lipids derived from the 20-carbon essential fatty acids (LCPUFA) and are involved in all aspects of the immune response. Omega -3 (ω3) fatty acids, Eicosapentaenoic acid (EPA) and Docosapentaenoic acid (DPA), Docosahexanoic acid (DHA) and Lipoxin A4 (LPA4) are anti-inflammatory, whilst the ω6-fatty acids Arachidonic acid (AA), 13-(S)hydroxyoctadecadienoic acid [13(S)HODE], 12(S)-hydroxyeicosatetraenoic acid(12(S)HETE),  Thromboxane B2 (TXB2), Prostaglandin F2α (PGF2α) and 6-Keto-Prostaglandin F1α (6kPGF1α) are pro-inflammatory. Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS) allows contemporaneous analyses of multiple prostanoids by stable isotope determination from 3mm dried whole blood spots. This method is novel in JIA and may find biomarkers which can help predict disease activity and treatment response with greater accuracy than current methods.

Methods:

Samples of whole blood from 115 JIA patients and 6 healthy siblings (HC) were collected onto specially prepared filter papers and analysed using LC-MSMS.

Results:

 The JIA M:F ratio was 1:1.4, the average age at study entry (9.4 ± 5.0 y), average disease duration (56.1 ± 46.1 m). None of the participants was taking fish oil.

Cross-sectional analysis

• 13(S)HODE and DHA levels were significantly different between JIA patient groups (p=0.05 for both)
• In general, there were significantly lower levels of pro-inflammatory prostanoids in JIA than in HC, particularly in polyarthritis
• JADAS correlated positively with PGB2 in all JIA sub-groups (p=0.046).  

Longitudinal analysis

• Within subject comparisons
•  Levels of AA (p=0.03), Leukotriene B4 (LTB4, p=0.003) and TBX2 (p=0.02) were all significantly lower in patients with active vs inactive disease (JADAS ≥1 vs <1)
• LPA4 levels were higher in patients with active disease (p=0.004)
• Between subject comparisons
•  13-S-HODE was reduced in patients with active disease (p=0.004)
• Correlations between changes in prostanoid levels, irrespective of disease activity (within subjects), showed combined changes in pro-and anti-inflammatory prostanoids:
• Increases in EPA correlated positively with higher levels of 13(S)HODE, 12(S)HETE, LTB4, TBX2, 6κPGF1α, (p<0.05 for all) as well as with increased LPA4 (p<0.0001)
• Increases in LPA4 correlated positively with DPA, and 6κPGF1α and negatively with AA, 15(S) HETE and TBX2 (p<0.0001 for all)
• There were no correlations between changes in ESR or CRP and those in prostanoids.

Conclusion:

In our cohort, we found that pro-inflammatory prostanoids were, in general, decreased in patients with active disease and in comparison to healthy controls. Increased EPA and LPA4 production were strongly associated with these changes.  These are novel findings and likely reflect the degree to which pro-resolving prostanoids are produced to control the inflammatory response in JIA over time. Prostanoid levels appear more sensitive to change than traditional laboratory markers of inflammation. Future analyses will include more detailed investigation of the prostanoids involved in the active resolution of inflammation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/fatty-acid-profiling-in-juvenile-idiopathic-arthritis-the-balance-between-pro-inflammatory-and-pro-resolving-prostanoids/