Sphingosine-1-phosphate in anti-neutrophil cytoplasmic antibody-associated vasculitis: coagulation-related clinical indicators and complications

Wu, Kaili; Liang, Qinghui; Ding, Na; Li, Bowei; Hao, Jian

doi:10.1042/bsr20200157

Cited by 3 publications

(11 citation statements)

References 53 publications

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“…65 RA was investigated in 10 study groups, [66][67][68][69][70][71]73,79,88,91 SLE in nine, 66,72,75,[81][82][83]86,87,89 BD in three, 62,76,77 AAV in three, 78,83,84 spondyloarthritis (SpA) and AS in three, 70,85,90 SSc in two, 64,74 OA in two, 65,70 gout in one, 80 crystal arthritis in one, 70 Takayasu arteritis (TA) in one, 63 and primary Sjögren's Syndrome (pSS) in one. 92 Twenty-four studies were prospective [62][63][64][65][66][67][68][69][70][71][73][74][75]…”

Section: Resultsmentioning

confidence: 99%

A systematic review and meta‐analysis of the association between the D‐dimer and rheumatic diseases

Zinellu,

Mangoni

2024

Immunity Inflam & Disease

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IntroductionThere is good evidence that specific autoimmune rheumatic diseases (RDs), for example, rheumatoid arthritis and systemic lupus erythematosus (SLE), are associated with a state of hypercoagulability and an increased risk of venous thromboembolism (VTE). However, limited information regarding this association is available for other autoimmune or autoinflammatory RDs. We sought to address this issue by conducting a systematic review and meta‐analysis of the association between the d‐dimer, an established marker of hypercoagulability and VTE, and RDs and the possible clinical and demographic factors mediating this association.MethodsWe searched the electronic databases PubMed, Web of Science, and Scopus from inception to January 31, 2024. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively.ResultsIn 31 studies selected for analysis (2724 RD patients and 3437 healthy controls), RD patients had overall significantly higher d‐dimer concentrations when compared to controls (standard mean difference = 0.93, 95% CI 0.76−1.10, p < .001; I2 = 86.1%, p < .001; moderate certainty of evidence). The results were stable in a sensitivity analysis. Significant associations were observed between the effect size of the between‐group differences in d‐dimer concentration and age, specific RD and RD category, RD duration, fibrinogen, plasminogen activator inhibitor, C‐reactive protein, and erythrocyte sedimentation rate.ConclusionsOverall, patients with RDs have significantly higher d‐dimer concentrations when compared with healthy controls, indicating a state of hypercoagulability. The alterations in d‐dimer concentrations are mediated by age, specific RD and RD category, RD duration, and markers of anticoagulation and inflammation. Further research is warranted to investigate d‐dimer concentrations across the spectrum of RDs and their utility in predicting and managing VTE in these patients (PROSPERO registration number: CRD42024517712).

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Section: Resultsmentioning

confidence: 99%

A systematic review and meta‐analysis of the association between the D‐dimer and rheumatic diseases

Zinellu,

Mangoni

2024

Immunity Inflam & Disease

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“…S1P, in particular, appears to regulate both the immune response and inflammation [ 70 , 71 ]. It binds to specific cell receptors participating in cell growth, angiogenesis, proliferation, lymphocyte migration and inhibition of apoptosis [ 72 , 73 ]. Today, both the S1P and the S1P receptor (S1PR) are considered as novel and interesting therapeutic targets for AIRDs [ 72 ].…”

Section: Ceramidesmentioning

confidence: 99%

“…It binds to specific cell receptors participating in cell growth, angiogenesis, proliferation, lymphocyte migration and inhibition of apoptosis [ 72 , 73 ]. Today, both the S1P and the S1P receptor (S1PR) are considered as novel and interesting therapeutic targets for AIRDs [ 72 ]. In contrast, other ceramides, such as dihydroceramides and sphinganine, are considered as anti-inflammatory since they act in reducing inflammation [ 74 ].…”

Section: Ceramidesmentioning

confidence: 99%

“…Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis, with three distinct clinical types, namely the granulomatous one with polyangiitis (GPA), the eosinophilic granulomatous polyangiitis (EGPA) and the microscopic polyangiitis (MPA) [ 162 ]. Patients with AAV are in a hypercoagulable state [ 72 , 163 ], exhibiting more frequent thromboembolisms and cardiovascular and cerebrovascular events compared to healthy volunteers [ 164 ]. This is due to several factors, one of which involves the S1P.…”

Section: Evidence Regarding Ceramides In Patients With Airdsmentioning

confidence: 99%

“…This is due to several factors, one of which involves the S1P. Higher plasma concentrations of S1P stimulate neutrophils and the production of thrombin, which can dismantle endothelial cells’ integrity during coagulation [ 72 , 165 , 166 ]. Hao and associates [ 70 ] compared the levels of S1P in patients with AAV, when in active disease and when in remission, with the sample comprising the cases and the control patients, at the same time ( Table 8 ).…”

Section: Evidence Regarding Ceramides In Patients With Airdsmentioning

confidence: 99%

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Ceramides in Autoimmune Rheumatic Diseases: Existing Evidence and Therapeutic Considerations for Diet as an Anticeramide Treatment

et al. 2023

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Autoimmune rheumatic diseases (AIRDs) constitute a set of connective tissue disorders and dysfunctions with akin clinical manifestations and autoantibody responses. AIRD treatment is based on a comprehensive approach, with the primary aim being achieving and attaining disease remission, through the control of inflammation. AIRD therapies have a low target specificity, and this usually propels metabolic disturbances, dyslipidemias and increased cardiovascular risk. Ceramides are implicated in inflammation through several different pathways, many of which sometimes intersect. They serve as signaling molecules for apoptosis, altering immune response and driving endothelial dysfunction and as regulators in the production of other molecules, including sphingosine 1-phosphate (S1P) and ceramide 1-phosphate (C1P). With lipid metabolism being severely altered in AIRD pathology, several studies show that the concentration and variety of ceramides in human tissues is altered in patients with rheumatic diseases compared to controls. As a result, many in vitro and some in vivo (animal) studies research the potential use of ceramides as therapeutic targets in rheumatoid arthritis (RA), ankylosing spondylitis, systemic lupus erythematosus, fibromyalgia syndrome, primary Sjögren’s syndrome, systemic sclerosis, myositis, systemic vasculitis and psoriatic arthritis. Furthermore, the majority of ceramide synthesis is diet-centric and, as a result, dietary interventions may alter ceramide concentrations in the blood and affect health. Subsequently, more recently several clinical trials evaluated the possibility of distinct dietary patterns and nutrients to act as anti-ceramide regimes in humans. With nutrition being an important component of AIRD-related complications, the present review details the evidence regarding ceramide levels in patients with AIRDs, the results of anti-ceramide treatments and discusses the possibility of using medical nutritional therapy as a complementary anti-ceramide treatment in rheumatic disease.

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Identification of Plasma Metabolomic Biomarkers of Juvenile Idiopathic Arthritis

Kumar,

Tatarian,

Shakhnovich

et al. 2024

Metabolites

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Identification of disease and therapeutic biomarkers remains a significant challenge in the early diagnosis and effective treatment of juvenile idiopathic arthritis (JIA). In this study, plasma metabolomic profiling was conducted to identify disease-related metabolic biomarkers associated with JIA. Plasma samples from treatment-naïve JIA patients and non-JIA reference patients underwent global metabolomic profiling across discovery (60 JIA, 60 non-JIA) and replication (49 JIA, 38 non-JIA) cohorts. Univariate analysis identified significant metabolites (q-value ≤ 0.05), followed by enrichment analysis using ChemRICH and metabolic network mapping with MetaMapp and Cytoscape. Receiver operating characteristic (ROC) analysis determined the top discriminating biomarkers based on area under the curve (AUC) values. A total of over 800 metabolites were measured, consisting of 714 known and 155 unknown compounds. In the discovery cohort, 587 metabolites were significantly altered in JIA patients compared with the reference population (q < 0.05). In the replication cohort, 288 metabolites were significantly altered, with 78 overlapping metabolites demonstrating the same directional change in both cohorts. JIA was associated with a notable increase in plasma levels of sphingosine metabolites and fatty acid ethanolamides and decreased plasma levels of sarcosine, iminodiacetate, and the unknown metabolite X-12462. Chemical enrichment analysis identified cycloparaffins in the form of naproxen and its metabolites, unsaturated lysophospholipids, saturated phosphatidylcholines, sphingomyelins, ethanolamines, and saturated ceramides as the top discriminating biochemical clusters. ROC curve analysis identified 11 metabolites classified as highly discriminatory based on an AUC > 0.90, with the top discriminating metabolite being sphinganine-1-phosphate (AUC = 0.98). This study identifies specific metabolic changes in JIA, particularly within sphingosine metabolism, through both discovery and replication cohorts. Plasma metabolomic profiling shows promise in pinpointing JIA-specific biomarkers, differentiating them from those in healthy controls and Crohn’s disease, which may improve diagnosis and treatment.

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Sphingosine-1-phosphate in anti-neutrophil cytoplasmic antibody-associated vasculitis: coagulation-related clinical indicators and complications

Cited by 3 publications

References 53 publications

A systematic review and meta‐analysis of the association between the D‐dimer and rheumatic diseases

A systematic review and meta‐analysis of the association between the D‐dimer and rheumatic diseases

Ceramides in Autoimmune Rheumatic Diseases: Existing Evidence and Therapeutic Considerations for Diet as an Anticeramide Treatment

Identification of Plasma Metabolomic Biomarkers of Juvenile Idiopathic Arthritis

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