Dataset Information

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

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.

SUBMITTER: Harden OC

PROVIDER: S-EPMC7546393 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Harden Olivia C OC Hammad Samar M SM

Frontiers in immunology 20200925

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), Systemi ...[more]

PMID: 33101319

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Project description:This study aims to analyze the relationship between pregnancy and lupus, and explore the risk factors that adversely affect maternal and infant outcomes.The pregnancy outcomes in 112 pregnant females (mean age 24.3±2.8 years; range 20 to 35 years) with systemic lupus erythematosus (SLE) were retrospectively analyzed. Pregnancy outcomes before and after pregnancy were compared, and the associations with lupus nephritis, positive anti-Ro/SSA antibody, positive La/SSB antibody, complement 3 and complement 4, high blood pressure, positive anti- cardiolipin (aCL) antibody, Raynaud's phenomenon, and lupus recurrence were evaluated. Factors contributing to adverse outcomes were analyzed using multinomial logistic regression.The live birth rate in females diagnosed with SLE before a pregnancy was higher than that in females diagnosed with SLE after a pregnancy. The fetal mortality rate in females diagnosed with SLE after a pregnancy was higher than that in females diagnosed with SLE before a pregnancy. However, the abortion rate in females diagnosed with SLE before a pregnancy was also significantly higher than that in females diagnosed with SLE after a pregnancy. The incidence of preterm birth in females diagnosed with SLE after a pregnancy was higher than that in females diagnosed with SLE after a pregnancy. Preterm birth was more likely to occur in females positive for Ro/SSA antibody. Patients with hypertension and Raynaud's phenomenon had a higher risk of intrauterine growth retardation. In addition, the presence of aCL antibody was associated with pregnancy loss. Multinomial logistic regression analysis showed that many factors might be associated with adverse pregnancy outcomes, including lupus nephritis, positive Ro/SSA antibody, positive La/SSB antibody, complement 3 and complement 4, positive aCL antibody, lupus recurrence, hypertension, and Raynaud's phenomenon.Lupus nephritis, Ro/SSA antibody, aCL antibody, hypertension, Raynaud's phenomenon, and lupus recurrence are important factors associated with adverse pregnancy outcomes.

Project description:ObjectiveAt least half of patients with systemic lupus erythematosus (SLE) develop organ damage as a consequence of autoimmune disease or long-term therapeutic steroid use. This study synthesised evidence on the association between organ damage and mortality in patients with SLE.DesignSystematic review and meta-analysis.MethodsElectronic searches were performed in PubMed, Embase, Cochrane Library and Latin American and Caribbean Health Sciences Literature for observational (cohort, case-control and cross-sectional) studies published between January 2000 and February 2017. Included studies reported HRs or ORs on the association between organ damage (measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score) and mortality. Study quality was assessed using the modified Newcastle-Ottawa assessment. Pooled HRs were obtained using the DerSimonian and Laird random-effects model. Heterogeneity was assessed using the Cochrane Q (Q) and I2 statistics.ResultsThe search yielded 10 420 articles, from which 21 longitudinal studies were selected. Most studies (85%) were of high quality. For 10 studies evaluating organ damage (SDI) as a continuous variable and reporting HR as a measure of association, a 1-unit increase in SDI was associated with increased mortality; pooled HR was 1.34 (95% CI: 1.24 to 1.44, p<0.001; Q p=0.027, I2=52.1%). Exclusion of one potential outlying study reduced heterogeneity with minimal impact on pooled HR (1.33 (95% CI: 1.25 to 1.42), p<0.001, Q p=0.087, I2=42.0%). The 11 remaining studies, although they could not be aggregated because of their varying patient populations and analyses, consistently demonstrated that greater SDI was associated with increased mortality.ConclusionsOrgan damage in SLE is consistently associated with increased mortality across studies from various countries. Modifying the disease course with effective therapies and steroid-sparing regimens may reduce organ damage, improve outcomes and decrease mortality for patients with SLE.

Dataset Information

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

Publications

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

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