Session Title: Pediatric Rheumatology – Pathogenesis and Genetics Poster
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Juvenile Idiopathic Arthritis (JIA) is often accompanied by inflammation of the joints. The mechanisms involved in the inflammation in JIA are incompletely understood. Several cells and soluble mediators, including lipid mediators regulate the course of inflammation. Lipid mediators such as prostaglandins and leukotrienes, derived from arachidonic acid have mostly pro-inflammatory properties, while specialized pro-resolving lipid mediators (SPM) derived from docosahexaenoic and eicosapentaenoic acid have anti-inflammatory/pro-resolving actions. Both types of lipid mediators are generated by cyclooxygenases and lipoxygenases. It is currently unknown which lipid pathways are present in synovial fluid (SF) of JIA.
The aim of this pilot study is to identify the lipid mediators present in the SF of JIA to gain a better understanding of the inflammatory process in the JIA joint.
Ten anonymized JIA SF were obtained as leftover material from arthrocentesis from patients visiting the outpatient unit of the Pediatrics department in the LUMC. Clinical data such as diagnosis, age, gender and BMI were provided. Different immune cell populations in the SF were identified using flow cytometry. The presence of 60 different lipid mediators was determined in SF using liquid chromatography-mass spectrometry (LC-MS/MS) after hyaluronidase treatment, protein precipitation using methanol followed by enrichment for polar lipids by solid-phase extraction.
Major immune cell populations identified in SF were monocytes, neutrophils, T cells and B cells. In general, the abundance of these populations was comparable in all JIA samples, except for neutrophils, which were more prevalent in patients that showed enthesitis.
Using LC-MS/MS, we detected arachidonic acid and several of its derivatives in SF. Pro-inflammatory lipid mediators and their precursors derived from arachidonic acid and generated by cyclooxygenases (thromboxane B2, prostaglandin E2) and 5-lipoxygenase (5-HETE and leukotriene B4) were detected in most of the samples. Interestingly, precursors of arachidonic acid-derived anti-inflammatory lipids generated by 15-lipoxygenase (15-HETE) and 12-lipoxygenase (12-HETE) were also detected. However, despite the high levels of docosahexaenoic acid (a precursor of SPM) present in all SF, we did not detect any of its anti-inflammatory lipoxygenase derivatives or SPM. Moreover, only low levels of eicosapentaenoic acid (a precursor of SPM) were detected, but none of its derivatives.
Our data suggests that the enzymatic pathways involved in both pro-inflammatory and anti-inflammatory lipid mediator production are active in JIA. However, they appear to preferentially handle arachidonic acid above docosahexaenoic and eicosapentaenoic acid to generate downstream metabolites.
To cite this abstract in AMA style:von Hegedus JH, Madari QSR, Hissink Muller PCE, Kloppenburg M, Toes R, Giera M, Huizinga T, ten Cate R, Ioan-Facsinay A. Characterisation of Lipid Mediator Profile and Immune Cells in Synovial Fluid of Juvenile Idiopathic Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/characterisation-of-lipid-mediator-profile-and-immune-cells-in-synovial-fluid-of-juvenile-idiopathic-arthritis/. Accessed March 3, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterisation-of-lipid-mediator-profile-and-immune-cells-in-synovial-fluid-of-juvenile-idiopathic-arthritis/