Changes in Plasma Phospholipid Metabolism Are Associated with Clinical Manifestations of Systemic Sclerosis

Abstract

Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and/or internal organs, causing a decrease in quality of life and survival. There is no causative therapy, and the pathophysiology of the SSc remains unclear. Studies showed that lipid metabolism was relevant for autoimmune diseases, but little is known about the role of lipids in SSc. In the present study, we sought to explore the phospholipid profile of SSc by using the lipidomics approach. We also aimed to analyze lipidomics results for different clinical manifestations of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry for the lipidomic profiling of plasma samples from patients with SSc. Our study showed, for the first time, significant changes in the level of phospholipids such as plasmalogens and sphingomyelins from the plasma of SSc patients as compared to controls. Phosphatidylcholine plasmalogens species and sphingomyelins were significantly increased in SSc patients as compared to controls. Our results also demonstrated a significant association of changes in the metabolism of phospholipids (phosphatidylcholine and phosphatidylethanolamine plasmalogens species and sphingomyelins) with different clinical manifestations of SSc. Further lipidomic studies might lead to the detection of lipids as new biomarkers or therapeutic targets of SSc.

Whole Blood and Plasma-Based Lipid Profiling Reveals Distinctive Metabolic Changes in Systemic Lupus Erythematosus and Systemic Sclerosis

“…Our findings align with the existing literature regarding the increase of SM in the plasma of SS patients. 23 Elevated levels of SM species may be associated with atherogenesis. The hydrolysis of SM into ceramides (Cer) in atherogenic lipoproteins like LDL leads to lipoprotein aggregation and fusion, resulting in the formation of large lipoprotein aggregates resembling those found in extracellular regions of atherosclerotic lesions.…”

“…On the other hand, SM­(d34:0), SM­(d40:2), and SM­(d38:1) exhibited statistical differences only between controls vs SS and SS vs SLE, indicating that the plasma profile of SM in SLE does not undergo significant alterations compared to controls (Figure ). Our findings align with the existing literature regarding the increase of SM in the plasma of SS patients . Elevated levels of SM species may be associated with atherogenesis.…”

“…22 PC plasmalogen species and SM were found to be significantly increased in the plasma of SS patients, while PE plasmalogen species were significantly reduced. 23 The profiles of plasma FA and acylcarnitine (CAR) are also altered, with reported increases of FA C12:0, C14:0, and C20:0, CAR and CAR 5:0, and reduction in CAR 8:0 and CAR 16:0. 24 Other lipid molecule characteristics of inflammatory and oxidative stress conditions, such as leukotrienes and isoprostanes, have also been found to be elevated in both diseases.…”

“…Nevertheless, increased serum levels of lysophosphatidic acid (20:4) and sphingosine 1-phosphate have been reported . PC plasmalogen species and SM were found to be significantly increased in the plasma of SS patients, while PE plasmalogen species were significantly reduced . The profiles of plasma FA and acylcarnitine (CAR) are also altered, with reported increases of FA C12:0, C14:0, and C20:0, CAR and CAR 5:0, and reduction in CAR 8:0 and CAR 16:0 .…”

Ceramides in Autoimmune Rheumatic Diseases: Existing Evidence and Therapeutic Considerations for Diet as an Anticeramide Treatment

“…In this manner, the important role of ceramides in tissue fibrosis identified them as a promising target for the development of novel antifibrotic treatments [ 146 , 147 ]. In a case-control study of patients having a SSc diagnosis, Geroldinger-Simić and associates [ 148 ] revealed differences in the level of phospholipids (plasmalogens and SM) in the plasma of patients, compared to healthy controls ( Table 6 ). Additionally, they demonstrated that distinct clinical manifestations of SSc are associated with different alterations in the metabolism of phospholipids.…”