Plasma Sphingolipids as Biomarkers for the Early Diagnosis of Atherosclerosis in Systemic Lupus Erythematosus

Sphingolipids may have potential as an early diagnostic tool of atherosclerosis in African American patients with systemic lupus erythematosus (SLE), according to study findings published in Frontiers in Immunology.

Research has shown that patients with SLE are at an increased risk for cardiovascular disease (CVD); therefore, researchers of the current study sought to identify the predictive value of sphingolipids in measuring the severity of atherosclerosis in African American patients with SLE.

The prospective cohort study was conducted at the Medical University of South Carolina Clinical Chemistry, Hematology, and Immunology Laboratories. Researchers included 39 African American patients with SLE, 35 (89.7%) of whom were women. Mean age at baseline was 43 years; average duration of SLE was 10 years.

Plasma samples from a group of African American patients with SLE with a well-defined carotid atherosclerotic plaque burden were examined for sphingolipids using targeted mass spectroscopy. The plasma concentrations of individual species of 5 classes of sphingolipids were measured: ceramides and sphingoid bases; sphingosine and dihydrosphingosine and their phosphates; sphingomyelin; glycosphingolipid lactosylceramide; and glycosphingolipid hexosylceramide. Carotid ultrasonography was performed to establish the total plaque area (TPA) in carotids at baseline (ie, visit 1) and 1 year later (ie, visit 2).

Results of the study showed that serum triglyceride and cholesterol levels in lipoprotein fractions were within the normal range. Mean total cholesterol was 10% lower among patients with SLE compared with matched control participants. Of note, hydroxychloroquine (HCQ), which may have been used as a treatment in patients with SLE prior to baseline, was previously shown to lower total cholesterol levels by approximately 15% after initiating therapy.

Mean sphingolipid levels did not differ according to HCQ use or prednisone dose. For participants (n=9) who received treatment with angiotensin-converting enzyme (ACE) inhibitors, levels of C14:0, C16:0, C18:0, C22:1, C24:1 ceramides and C16:0 ceramide/S1P ratio were significantly higher than in those who did not receive treatment with ACE inhibitors (P <.05). Among participants (n=3) who received angiotensin II receptor blockers (ARBs), C16:0 ceramide/C24:0 ceramide ratios were significantly higher (P <.05), but levels of C20:0 and C24:0 SM were significantly lower (P <.05) than among those who did not receive ARBs.

Data revealed that at baseline, TPA and C3 values were inversely correlated with most lactoceramide species. However, at the 1-year follow-up visit, changes in TPA were positively correlated with the lactoceramide species. Further, no correlation was observed between low-density lipoprotein cholesterol levels and lactoceramide species.

One of the main study limitations was the fact that because only 4 patients in the study were receiving treatment with statins, it was difficult to determine the effect of statins on atherosclerosis development among the patients with SLE.

The researchers concluded, “Longitudinal studies are warranted to proof the potential sphingolipid markers for early diagnosis of SLE comorbidities, including CVD.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 

Reference

Hammad SM, Harden OC, Wilson DA, Twal WO, Nietert PJ, Oates JC. Plasma sphingolipid profile associated with subclinical atherosclerosis and clinical disease markers of systemic lupus erythematosus: potential predictive value. Front Immunol. Published online July 21, 2021. doi:10.3389/fimmu.2021.694318