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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.

SUBMITTER: Geroldinger-Simic M

PROVIDER: S-EPMC8625116 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVE: To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features. METHODS: We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay. RESULTS: We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33 ± 4.50), 64 first-degree relatives (mean age 39.95 ± 5.66), and 57 healthy (mean age 19.30 ± 4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their first-degree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels. CONCLUSION: Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares.

Project description:Background Cardiovascular involvement in systemic sclerosis (SSc) comprises a wide range of manifestations with prevalence and incidence that remain uncertain. Methods and Results In the Danish administrative registries between 1995 and 2015, all patients aged ?18 years with a first diagnosis of SSc were matched by age and sex with controls (1:5) from the general population. Prevalence of cardiovascular diseases at the time of the SSc diagnosis and incidence during follow-up were assessed by in- and outpatient discharge diagnoses. Conditional logistic and Cox proportional hazards regression models were used respectively to calculate odds ratios for prevalent cardiovascular diseases and hazard ratios (HRs) for incident diseases associated with SSc. Patients with SSc (n=2778; 76% women; mean±SD age: 55±15 years) had more established cardiovascular risk factors than their respective controls at baseline, including greater prevalence of hypertension (31.2% versus 21.0%, P<0.0001) and treated dyslipidemia (9.8% versus 8.5%, P=0.02). SSc was associated with an increased relative risk of developing most cardiovascular diseases, including myocardial infarction (HR: 2.08; 95% CI, 1.65-2.64), peripheral vascular disease (HR: 5.73; 95% CI, 4.63-7.09), pulmonary hypertension (HR: 21.18; 95% CI, 14.73-30.45), mitral regurgitation (HR: 4.60; 95% CI, 3.12-6.79), aortic regurgitation (HR: 3.78; 95% CI, 2.55-5.58), aortic stenosis (HR: 2.99; 95% CI, 2.25-3.97), pericarditis (HR: 8.78; 95% CI, 4.84-15.93), heart failure (HR: 2.86; 95% CI, 2.43-3.37), atrial fibrillation (HR: 1.75; 95% CI, 1.51-2.04), and venous thromboembolism (HR: 2.10; 95% CI, 1.65-2.67). Additional adjustment for medications and comorbidities yielded results similar to the main analyses. Conclusions In this nationwide study, SSc was associated with greater risks of distinct cardiovascular diseases for patients than for matched controls, suggesting a significant disease-related adverse impact across the vascular bed and specific cardiac structures.

Project description:Systemic sclerosis (SSc) is an autoimmune disease initially recognized by hand involvement due to characteristic Raynaud's phenomenon (RP), puffy hands, skin thickening, and contractures resembling claw deformities. SSc contributes to hand impairment through inflammatory arthritis, joint contractures, tendon friction rubs (TFRs), RP, digital ulcers (DU), puffy hands, skin sclerosis, acro-osteolysis, and calcinosis. These manifestations, which often co-exist, can contribute to difficulty with occupational activities and activities of daily living (ADL), which can result in impaired quality of life. However, despite this knowledge, most diagnostic and treatment principles in SSc are focused on visceral manifestations due to known associations with morbidity and mortality. Treatment of inflammatory arthritis is symptom based and involves corticosteroids ?10mg daily, methotrexate, tumor necrosis factor inhibitors, tocilizumab, and abatacept. Small joint contractures are managed by principles of occupational hand therapy and rarely surgical procedures. TFRs may be treated similar to inflammatory arthritis with corticosteroids. All patients with RP and DU should keep digits covered and warm and avoid vasoconstrictive agents. Pharmacologic management of RP begins with use of calcium channel blockers, but additional agents that may be considered are fluoxetine and phosphodiesterase 5 (PDE5) inhibitors. DU management also involves vasodilators including calcium channel blockers and PDE5 inhibitors; bosentan has also been shown to prevent DU. In patients with severe RP and active DU, intravenous epoprostenol or iloprost can be used and surgical procedures, such as botulinum injections and digital sympathectomies, may be considered. For those with early diffuse cutaneous SSc needing immunosuppression for skin sclerosis, methotrexate or mycophenolate mofetil can be used, but the agent of choice depends on co-existing manifestations, such as inflammatory arthritis and/or lung involvement. Various pharmacologic agents for calcinosis have been considered but are generally ineffective; however, surgical options, including excision of areas of calcinosis, can be considered. Overall management of hand impairment for all patients with SSc should include occupational hand therapy techniques such as range of motion exercises, paraffin wax, and devices to assist in ADL. Thus, treatment options for the various manifestations contributing to hand impairment in SSc are limited and often modestly efficacious at best. Robust studies are needed to address the manifestations of SSc that contribute to hand impairment.

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

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