Session Title: Pediatric Rheumatology - Pathogenesis and Genetics
Session Type: Abstract Submissions (ACR)
The prostanoids are a family of biologically active lipids derived from the 20-carbon essential fatty acids (LCPUFA) all of which are involved in the inflammatory response. ω3-fatty acids, Eicosapentaenoic acid (EPA) and Docosapentaenoic acid (DPA), are anti-inflammatory, whilst the ω6-fatty acid, Arachidonic acid (AA), metabolites: 15-S-Hydroxyeicosatetraenoic acid [15(S)-HETE], Thromboxane B2 (TXB2), Prostaglandin F2α (PGF2α) and 6–Keto-Prostaglandin F1α (6-k-PGF1α) are pro-inflammatory. Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS) allows contemporaneous analyses of multiple prostanoids with high accuracy using small blood samples. This method has never been used previously to measure these analytes in JIA and may find biomarkers which can help us predict disease activity and treatment response.
We aim to measure prostanoid profiles in patients with JIA using LC-MSMS.
Samples from 55 JIA patients (26 polyarthritis, 29 oligoarthritis) and 6 healthy siblings of JIA patients were collected onto specially prepared filter papers and analysed using LC-MSMS.
The M:Fratio was 1:3, the average age at study entry (9.4 ± 5.0 y), average disease duration (44.7 ± 41.5 m), with 83.6% receiving treatment with NSAID, and 38.2% with Methotrexate (MTX).
15(S)-HETE levels were significantly higher in oligoarthritis than polyarthritis patients (Mann-Whitney U, p=0.046). Spearman rank correlations showed that MTX treatment correlated positively with 15(S)-HETE (p=0.01, R=0.493) but correlated negatively with TXB2 (p=0.004, R=-0.514), Leflunomide treatment correlated negatively with PGF2α (p=0.022, R=-0.448), Etanercept treatment correlated negatively with PGF2α, (p=0.013, R=-0.481) and correlated positively with 6-k-PGF1α (p=0.0216, R=0.451).
Stepwise linear regression showed TXB2 levels to be significantly higher in healthy controls compared to JIA patients (p=0.011) and JIA patients on MTX had significantly higher EPA levels (p=0.017) and lower AA:EPA ratios (p=0.011). 6-k-PGF1α level increased by 0.37nM in JIA patients with every extra month of disease (p=0.022) and DPA level reduced by 0.09nM with every point rise in Juvenile Arthritis Disease Activity Score (p=0.032).
We have been able to determine prostanoid profiles from whole blood using LC-MSMS in patients with JIA. Treatment with MTX increases the levels of anti-inflammatory prostanoids. This relationship has not been demonstrated previously.
NSAIDs are the mainstay of treatment in patients with JIA and resulted in lower TXB2 levels compared to healthy controls.
15(S)-HETE has been identified as a potential biomarker of disease activity in JIA
However, disease progression appears to continue in JIA despite treatment as shown by the elevation in 6-k-PGF1α levels. We are currently performing longitudinal analyses to elucidate the relationships between prostanoid profiles and disease subtype, activity and medication response.
W. T. Cham,
C. A. Boros,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/fatty-acid-profiling-potential-new-biomarkers-in-juvenile-idiopathic-arthritis-pilot-study/