Imbalance Between Omega-6- and Omega-3-Derived Bioactive Lipids in Arthritis in Older Adults

: Elderly-onset RA (EORA) and polymyalgia rheumatica (PMR) are common rheumatic diseases in the elderly. Oxylipins are bioactive lipids derived from omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) that serve as activators or suppressors of systemic inflammation. We hypothesized that arthritic symptoms in the elderly were related to oxylipins-related perturbations. Arthritis in the Elderly (ARTIEL) is an observational prospective cohort with 64 patients >60 years of age with newly diagnosed arthritis. Patients' blood samples at baseline and 3 months posttreatment were compared with 18 controls. A thorough clinical examination was conducted. Serum oxylipins were determined by mass spectrometry. Data processing and statistical analysis were performed in R. Forty-four patients were diagnosed with EORA and 20 with PMR. At diagnosis, EORA patients had a mean DAS28CRP (Disease Activity Score 28 using C reactive protein) of 5.77 (SD, 1.02). 100% of PMR patients reported shoulder pain and 90% reported pelvic pain. Several n-6- and n-3-derived oxylipin species were significantly different between controls and arthritis patients. The ratio of n-3/n-6 PUFA was significantly downregulated in EORA but not in PMR patients as compared to controls. The top two candidates as biomarkers for differentiating PMR from EORA were 4-HDoHE, a hydroxydocosahexaenoic acid, and 8,15-dihydroxy-eicosatrienoic acid (8,15-diHETE). The levels of n-3 derived anti-inflammatory species increased in EORA after treatment. These results suggest that certain oxylipins may be key effectors in arthritis in the elderly and that the imbalance between n-6 and n-3 derived oxylipins might be related to pathobiology in this population.