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Abstract Number: 75

Elevated Oxylipin Profile in Autoantibody-Positive Individuals at-Risk of Developing Rheumatoid Arthritis

Vidyanand Anaparti1, Irene Smolik2, Tanja Winter3, Xiaobo Meng4, Harold Aukema3 and Hani El-Gabalawy4, 1Internal Medicine, University of Manitoba, Winnipeg, MB, Canada, 2Arthritis Center, University of Manitoba, Winnipeg, MB, Canada, 3Food and Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada, 4University of Manitoba, Winnipeg, MB, Canada

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Rheumatoid arthritis (RA)

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Session Information

Date: Sunday, October 21, 2018

Session Title: Rheumatoid Arthritis – Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Preclinical phase of rheumatoid arthritis (RA) is characterized by presence of autoantibodies, including anti-citrullinated protein antibodies (ACPA), years before disease onset. Epidemiological observations suggest that high levels of total ω-3 fatty acids are significantly associated with lowering RA transition rate in autoantibody-positive individuals[1]. Fatty acids (FA) and their oxygenated eicosanoid metabolites (oxylipins) regulate systemic inflammatory responses and pro-inflammatory gene expression leading to orchestration of chronic inflammatory cascade[2]. Over the last 15 years, we longitudinally followed genetically-susceptible Indigenous North American (INA) population with a disproportionately high RA risk (~2-3fold) and increased autoantibody prevalence. In this study, we examined the circulating levels of FA and their oxylipins in RA patients and their asymptomatic ACPA+ and ACPA- first-degree relatives (FDR) from this cohort to understand the role of these metabolites in preclinical RA pathogenesis.

Methods: Gas chromatography (GC) was used for FA estimation in serum samples from age-matched ACPA+ RA patients (N=10), ACPA- FDR (N=10), and ACPA+ FDR (N=53). Oxylipins were extracted and quantified using high performance liquid chromatography – tandem mass spectrometry (HPLC/MS/MS).

Results: We observed an overall increase in unsaturated and ω-6 FA levels in all the study subjects. The ω-3 index (% EPA + DHA) in these individuals was ~5-6% of total FA suggesting an intermediate risk category for coronary heart disease and inflammation. No significant differences were observed in circulating FA levels between RA patients and ACPA- FDRs. Serum eicosanoid profiling identified enrichment of 41 oxylipins (out of 77 mapped metabolites) in ACPA+ FDR compared to RA patients and ACPA- FDR (Mann-Whitney U test). Of these, 9-HODE and 13-HODE were significantly elevated in ACPA+ FDR compared to ACPA- FDR (~55-fold and ~41-fold respectively; P< 0.0000000001) and RA patients (~32-fold and ~22-fold respectively; P< 0.0000000001). While usage of NSAIDs had no effect on total oxylipin levels, samples stored at -20°C for >5yrs demonstrated significant oxylipin enrichment (***P=0.0006). After correcting for duration of storage effects, we still observed an elevated oxylipin profile in ACPA+ FDR compared to other groups.

Conclusion: Our study demonstrates a distinct FA and oxylipin profile in asymptomatic ACPA+ FDR of INA RA patients and suggests that changes in the specific eicosanoids and their oxygenated metabolites are involved in the development of ACPA and/or the transition to clinically imminent RA in ACPA+ individuals.

  1. Gan, R.W., et al., The association between omega-3 fatty acid biomarkers and inflammatory arthritis in an anti-citrullinated protein antibody positive population. Rheumatology (Oxford), 2017. 56(12): p. 2229-2236.
  2. Brouwers, H., et al., Lipid mediators of inflammation in rheumatoid arthritis and osteoarthritis. Best Pract Res Clin Rheumatol, 2015. 29(6): p. 741-55.

Disclosure: V. Anaparti, None; I. Smolik, None; T. Winter, None; X. Meng, None; H. Aukema, None; H. El-Gabalawy, None.

To cite this abstract in AMA style:

Anaparti V, Smolik I, Winter T, Meng X, Aukema H, El-Gabalawy H. Elevated Oxylipin Profile in Autoantibody-Positive Individuals at-Risk of Developing Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/elevated-oxylipin-profile-in-autoantibody-positive-individuals-at-risk-of-developing-rheumatoid-arthritis/. Accessed December 9, 2019.
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