Abstract
The pathogenesis of systemic lupus erythematosus (SLE) remains elusive. It appears that serum lipid metabolism is aberrant in SLE patients. Determination of lipid profiles in the serum of SLE patients may provide insights into the underlying mechanism(s) leading to SLE and may discover potential biomarkers for early diagnosis of SLE. This study aimed to identify and quantify the profile of serum lipids in SLE patients (N = 30) with our powerful multi-dimensional mass spectrometry-based shotgun lipidomics platform. Multivariate analysis in the form of partial least squares-discriminate analysis was performed, and the associations between the changed lipids with cytokines and SLE disease activity index (SLEDAI) were analyzed using a multiple regression method. The results of this study indicated that the composition of lipid species including diacyl phosphatidylethanolamine (dPE) (16:0/18:2, 18:0/18:2, 16:0/22:6, 18:0/20:4, and 18:0/22:6), 18:2 lysoPC (LPC), and ceramide (N22:0 and N24:1) was significantly altered in SLE patients with p < 0.05 and variable importance of the projection (VIP) > 1 in partial least squares-discriminate analysis (PLS-DA). There existed significant associations between IL-10, and both 18:0/18:2 and 16:0/22:6 dPE species with p < 0.0001 and predicting 85.7 and 95.8% of the variability of IL-10 levels, respectively. All the altered lipid species could obviously predict IL-10 levels with F (8, 21) = 3.729, p = 0.007, and R2 = 0.766. There was also a significant correlation between the SLEDAI score and 18:0/18:2 dPE (p = 0.031) with explaining 22.6% of the variability of SLEDAI score. Therefore, the panel of changed compositions of dPE and ceramide species may serve as additional biomarkers for early diagnosis and/or prognosis of SLE.
Highlights
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease that is characterized by the immune system attacking self healthy cells and tissues throughout the body, and mainly occurs in women of childbearing age [1]
We focused on the changes of lipids related with oxidative stress (including plasmalogens, lysophospholipids, and 4-hydroxy-2(E)-nonenal (HNE) species), which were identified and quantified using our multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) platform [20]
Aberrant lipid metabolism exists in systemic lupus erythematosus (SLE) patients due to its pathological factors, including varieties of autoantibodies, elevated oxidative stress, and dysfunction of lipoproteins
Summary
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease that is characterized by the immune system attacking self healthy cells and tissues throughout the body, and mainly occurs in women of childbearing age [1]. A “lupus pattern” of dyslipoproteinemia, which may be responsible for the development of premature atherosclerosis, has been identified in SLE patients with 7- to 50-fold increased age-specific incidence of cardiovascular disease [5]. This pattern was noted in both untreated pediatric and adult patients and further aggravated by disease activity, indicating SLE itself promotes a proatherogenic lipid profile [5,6]
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