Sphingolipids and Diagnosis, Prognosis, and Organ Damage in Systemic Lupus Erythematosus

Harden, Olivia C; Hammad, Samar M.

doi:10.3389/fimmu.2020.586737

Cited by 19 publications

(20 citation statements)

References 100 publications

(208 reference statements)

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“…Notably, KEGG analysis indicted that sphingolipid metabolism was the top most significant pathway impacted and associated with SLE and disease activity ( Figure 3B and Supplementary Data 3.1 ). Interestingly, a previous study suggested that sphingolipid metabolism may be a biomarker and therapeutic target for SLE ( 12 ). Consistently, we also observed that the expression of many metabolites in the sphingolipid pathway were gradually changed in SLE patients compared to HCs ( Figure 3C ).…”

Section: Resultsmentioning

confidence: 99%

Multi-Platform Omics Analysis Reveals Molecular Signatures for Pathogenesis and Activity of Systemic Lupus Erythematosus

et al. 2022

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Systemic lupus erythematosus (SLE) is a complex autoimmune disease with heterogeneous clinical manifestations and the pathogenesis of SLE is still unclear. Various omics results have been reported for SLE, but the molecular hallmarks of SLE, especially in patients with different disease activity, using an integrated multi-omics approach have not been fully investigated. Here, we collected blood samples from 10 healthy controls (HCs) and 40 SLE patients with different clinical activity including inactive (IA), low activity (LA), and high activity (HA). Using an integrative analysis of proteomic, metabolomic and lipidomic profiles, we report the multi-omics landscape for SLE. The molecular changes suggest that both the complement system and the inflammatory response were activated in SLEs and were associated with disease activity. Additionally, activation of the immunoglobulin mediated immune response were observed in the LA stage of the disease, however this immune response was suppressed slightly in the HA stage. Finally, an imbalance in lipid metabolism, especially in sphingolipid metabolism, accompanied with dysregulated apolipoproteins were observed to contribute to the disease activity of SLE. The multi-omics data presented in this study and the characterization of peripheral blood from SLE patients may thus help provide important clues regarding the pathogenesis of SLE.

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Section: Resultsmentioning

confidence: 99%

Multi-Platform Omics Analysis Reveals Molecular Signatures for Pathogenesis and Activity of Systemic Lupus Erythematosus

et al. 2022

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“…Studies in literature showed that sialoglyco-conjugates are abundant in kidneys, and they could determine SLE organ determinations [ 11 , 12 , 13 , 14 , 15 ]. Seromucoids are released in the early stages of inflammation, act as acute phase reactants, modulate immunity, maintain the barrier function of the capillaries by mediating sphingolipids metabolism [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…Seromucoids are released in the early stages of inflammation, act as acute phase reactants, modulate immunity, maintain the barrier function of the capillaries by mediating sphingolipids metabolism [ 12 ]. Some researchers consider plasma and urinary glycosphingolipids useful tools in the early identification of LN [ 13 , 14 , 15 ]. Circulating sphingolipids (ceramides, hexosil-ceramides) were increased, and sphingoid bases were decreased in SLE patients versus control.…”

Section: Discussionmentioning

confidence: 99%

“…Circulant glyco-proteins (orosomucoids or alpha-1-acid glycoprotein) have important functions in immune and inflammatory response and could play a primary role in SLE disease activity and relapse [ 11 , 12 ]. Glycosphingolipids are involved in autoimmune diseases pathogenesis and renal disfunctions [ 13 , 14 , 15 ]. These molecules were little investigated in lupus nephritis (LN) during years [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Sialoglyco-Conjugate Abnormalities, IL-6 Trans-Signaling and Anti-Ganglioside Immune Response—Potential Interferences in Lupus Nephritis Pathogenesis

2021

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We have investigated glycoconjugates sialization profile, endogen synthesis rate of antiganglioside antibodies (AGA), IL-6 signaling pathways correlated with activity disease in systemic lupus erythematous (SLE) and lupus nephritis (LN). Material and methods. A case-control study was developed and included 109 patients with SLE with or without renal impairment, 32 patients with IgA nephropathy and 60 healthy volunteers, clinically and paraclinically monitored. The following parameters were evaluated in volunteers serum: total sialic acid (TSA), orosomucoids, lipid bound sialic acid (LSA), interleukin-6 (IL-6), soluble factors IL-6R, gp130, anti –GM1, -GM2, -GM3, -GD1a, -GD1b, -GT1b, -GQ1b antigangliosides antibodies of IgG and IgM type. Results. Experimental data analysis showed: increase in synthesis rhythm of sialoglyco-conjugated in SLE (TSA increased in SLE and LN compared to control), accelerated catabolism of LSA in LN (LSA/TSA ratio was higher in SLE and LN than in control group), overexpression of IL-6 mediated trans-signaling (sIL-6R/sgp 130 ratio was subunit in SLE and IgA nephropathy and superunit in LN), large AGA profile synthesis of IgM isotype (over 45.1% in SLE and over 20.7% in LN). Conclusions. Hypersialization, accelerated glycosphingolipids degradation, IL-6 trans-signaling amplify and AGA pattern could represent essential mechanisms in LN pathogenesis.

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“…Dysregulation of the sphingolipid pathway has been described in several inflammatory and immune-mediated diseases such as systemic lupus erythematosus (SLE) [96]. Data shows that SLE patients have higher plasma levels of total ceramides, including C16:0, C18:1, C18:0, C20:1, C:20:0, C24:1, and 26:1 Cer species [97]. As ceramides are associated with apoptosis and inflammation which are pathways to ATS and CAD, SLE patients have a raised risk of disease development [98].…”

Section: Cers Inhibitorsmentioning

confidence: 99%

Involvement of Ceramides in Non-Alcoholic Fatty Liver Disease (NAFLD) Atherosclerosis (ATS) Development: Mechanisms and Therapeutic Targets

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (ATS) are worldwide known diseases with increased incidence and prevalence. These two are driven and are interconnected by multiple oxidative and metabolic functions such as lipotoxicity. A gamut of evidence suggests that sphingolipids (SL), such as ceramides, account for much of the tissue damage. Although in humans they are proving to be accurate biomarkers of adverse cardiovascular disease outcomes and NAFLD progression, in rodents, pharmacological inhibition or depletion of enzymes driving de novo ceramide synthesis prevents the development of metabolic driven diseases such as diabetes, ATS, and hepatic steatosis. In this narrative review, we discuss the pathways which generate the ceramide synthesis, the potential use of circulating ceramides as novel biomarkers in the development and progression of ATS and related diseases, and their potential use as therapeutic targets in NAFDL-ATS development which can further provide new clues in this field.

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Sphingolipids and Diagnosis, Prognosis, and Organ Damage in Systemic Lupus Erythematosus

Cited by 19 publications

References 100 publications

Multi-Platform Omics Analysis Reveals Molecular Signatures for Pathogenesis and Activity of Systemic Lupus Erythematosus

Multi-Platform Omics Analysis Reveals Molecular Signatures for Pathogenesis and Activity of Systemic Lupus Erythematosus

Sialoglyco-Conjugate Abnormalities, IL-6 Trans-Signaling and Anti-Ganglioside Immune Response—Potential Interferences in Lupus Nephritis Pathogenesis

Involvement of Ceramides in Non-Alcoholic Fatty Liver Disease (NAFLD) Atherosclerosis (ATS) Development: Mechanisms and Therapeutic Targets

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