Oxidative stress leads to reduction of plasmalogen serving as a novel biomarker for systemic lupus erythematosus

Abstract

Oxidative stress is elevated in systemic lupus erythematosus (SLE) patients, and associated extensively with SLE pathogenesis. However, no common indicators of oxidative stress are yet in routine clinical use because of their instability, nonspecificity, and non-representation of all SLE symptoms. Moreover, the method for reproducible analysis of reactive oxygen species is still lacking. Lipids and their metabolites are essential components of biological systems, many of which serve as molecular targets of oxidative stress and play crucial roles in signaling, inflammation, and immune responses. Thus, determining the changed levels of lipids and their metabolites may serve the needs for SLE research. In the pilot study, shotgun lipidomics of sera from 30 SLE patients and 30 controls was performed and revealed a marked reduction of ethanolamine plasmalogen (pPE) species from 85.03±3.06 to 62.39±4.34 nmol/mL serum in controls and patients, respectively, accompanying significant increases in lysoPE (LPE) content (~46mol%) and 4-hydroxynonenal (an indictor of oxidative stress) in patients. Representative proinflammatory cytokines were also determined, revealing significant elevation of IL-6, IL-10, and TNF-α in SLE patients. Multivariate and multiple regression analyses showed for the first time that significant correlation among the SLE disease activity index, IL-10 levels, and pPE content exists, providing insights into SLE pathogenesis. The study also indicates that the changes of pPE (molecular targets of oxidative stress) and their peroxidation products may serve as novel biomarkers for diagnosis of SLE.