Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves multiple organs and disproportionality affects females, especially African Americans from 15 to 44 years of age. SLE can lead to end organ damage including kidneys, lungs, cardiovascular and neuropsychiatric systems, with cardiovascular complications being the primary cause of death. Usually, SLE is diagnosed and its activity is assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics Damage Index (SLICC/ACR), and British Isles Lupus Assessment Group (BILAG) Scales, which unfortunately often occurs after a certain degree of systemic involvements, disease activity or organ damage already exists. There is certainly a need for the identification of early biomarkers to diagnose and assess disease activity as well as to evaluate disease prognosis and response to treatment earlier in the course of the disease. Here we review advancements made in the area of sphingolipidomics as a diagnostic/prognostic tool for SLE and its co-morbidities. We also discuss recent reports on differential sphingolipid metabolism and blood sphingolipid profiles in SLE-prone animal models as well as in diverse cohorts of SLE patients. In addition, we address targeting sphingolipids and their metabolism as a method of treating SLE and some of its complications. Although such treatments have already shown promise in preventing organ-specific pathology caused by SLE, further investigational studies and clinical trials are warranted.
Highlights
Systemic lupus erythematosus (SLE) is a systemic, chronic autoimmune disease that could manifest in any organ system
The results showed that C16:0, C18:0, C20:0, and C24:1 ceramides were significantly elevated in the serum of lupus nephritis patients when compared to healthy controls (p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively), and to SLE patients without renal impairment (p < 0.01, p < 0.001, p < 0.001, and p < 0.001, respectively)
Since circulating ceramides are carried on lipoproteins, plasma C16:0, C18:0, C20:0, and C24:1 ceramides were, as expected, significantly elevated in lupus nephritis patients when compared to the healthy controls as well as SLE patients without renal impairment [53]
Summary
Systemic lupus erythematosus (SLE) is a systemic, chronic autoimmune disease that could manifest in any organ system. They measured 27 sphingolipids in serum samples of 107 female patients with SLE and 23 healthy controls and compared the values against the two commonly used SLE disease activity indices: SLAM and SLEDAI [41]. Checa et al [41] showed that following immunosuppressive treatment, sphingolipids were normalized to the levels seen in the healthy controls further supporting the use of sphingolipids as indices of SLE disease activity.
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