Lipidome changes indicate oxidative stress, inflammation, and specific loss of glycerophosphoserine inflammatory protection in patients with lupus.

Systemic lupus erythematosus (SLE, lupus) is a chronic autoimmune disease which has a complex etiology and suffers from both high false positive rates and false negative rates in diagnosis and classification. Substantial lipid changes have been observed previously in lupus patients, hence we carried out the most comprehensive lipidomics study in lupus to date using LipidMatch Flow. In this study, we investigated various sub-categories of lupus including lupus nephritis, active versus non-active lupus, as well as comparisons to non-lupus controls. A total of 1105 unique lipids spanning 36 lipid classes (or sub-classes) were annotated in blood plasma samples; of these, 111 lipids changed significantly between controls and active lupus. We determined for the first time, specific oxidized lipid markers, with oxidized triacylglycerols being the most significantly increased lipid sub-class in active lupus as compared to controls. Other indicators of oxidative stress included decreased lipids containing ether linkages and/or polyunsaturated fatty acids. Increased Cer(d18:1/16:0) and decreased C20-22 containing species (especially C20:4) indicated an inflammatory response in patients with active lupus. Furthermore, we determined a significant decrease of glycerophosphoserines, which are known inflammation suppressors, in patients with lupus and a decrease in Coenzyme Q9 and Q10; supplementation of lupus patients with Coenzyme Q10 has been shown to be protective [1-4]. Several unique lipids with unknown biology are also shown to significantly changed in active lupus. Many of these trends were also observed in non-active lupus, suggesting lipidomics related changes may occur early in disease development. In conclusion, this comprehensive lipidomics study expands our knowledge of the lipid alterations associated with lupus, providing insights into disease pathogenesis and depleted lipids, which could serve as therapeutic targets.