Plasma metabolomics analysis in sickle cell disease patients with albuminuria – an exploratory study

Elsherif, Laila; Pathmasiri, Wimal; McRitchie, Susan; Archer, David; Ataga, Kenneth I.

doi:10.1111/bjh.15592

Cited by 9 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reduced concentrations of sphingomyelin and ceramide have already been reported in the serum of patients with SCD [38]. Phosphatidylcholines were also found to be reduced in the erythrocytes from the mouse model [8]. However, in contrast with our results lysophosphatidylcholines were found to be increased in this study.…”

Section: Discussioncontrasting

confidence: 94%

“…The same group later showed that elevated concentrations of S1P mediated multi-tissue chronic inflammation through IL6 [7]. Lastly, a proton nuclear magnetic resonance ( 1 H-NMR)-based metabolomic approach was applied in the plasma of patients (n = 23) with SCD according to their level of albuminuria [8]. The concentration of six metabolites was modified according to albuminuria: betaine, proline, dimethylarginine, glutamate, leucine, and lysine.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Metabolomic Profiling of Plasma and Erythrocytes in Sickle Mice Points to Altered Nociceptive Pathways

Dembélé

Mintz

Veyrat-Durebex

et al. 2020

Cells

View full text Add to dashboard Cite

Few data-driven metabolomic approaches have been reported in sickle cell disease (SCD) to date. We performed a metabo-lipidomic study on the plasma and red blood cells of a steady-state mouse model carrying the homozygous human hemoglobin SS, compared with AS and AA genotypes. Among the 188 metabolites analyzed by a targeted quantitative metabolomic approach, 153 and 129 metabolites were accurately measured in the plasma and red blood cells, respectively. Unsupervised PCAs (principal component analyses) gave good spontaneous discrimination between HbSS and controls, and supervised OPLS-DAs (orthogonal partial least squares-discriminant analyses) provided highly discriminant models. These models confirmed the well-known deregulation of nitric oxide synthesis in the HbSS genotype, involving arginine deficiency and increased levels of dimethylarginines, ornithine, and polyamines. Other discriminant metabolites were newly evidenced, such as hexoses, alpha-aminoadipate, serotonin, kynurenine, and amino acids, pointing to a glycolytic shift and to the alteration of metabolites known to be involved in nociceptive pathways. Sharp remodeling of lysophosphatidylcholines, phosphatidylcholines, and sphingomyelins was evidenced in red blood cells. Our metabolomic study provides an overview of the metabolic remodeling induced by the sickle genotype in the plasma and red blood cells, revealing a biological fingerprint of altered nitric oxide, bioenergetics and nociceptive pathways.

show abstract

Section: Discussioncontrasting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Metabolomic Profiling of Plasma and Erythrocytes in Sickle Mice Points to Altered Nociceptive Pathways

Dembélé

Mintz

Veyrat-Durebex

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Proline levels are increased in both the SCA and SCA + HC groups. High proline levels in SCA individuals with albuminuria have been previously described 24 …”

Section: Resultsmentioning

confidence: 78%

Blood plasma metabolomics of children and adolescents with sickle cell anaemia treated with hydroxycarbamide: a new tool for uncovering biochemical alterations

et al. 2021

View full text Add to dashboard Cite

Summary Sickle cell anaemia (SCA) is a debilitating genetic haemoglobinopathy predominantly affecting the disenfranchised strata of society in Africa and the Americas. The most common pharmacological treatment for this disease is the administration of hydroxycarbamide (HC) for which questions remain regarding its mechanism of action, efficacy and long‐term toxicity specifically in paediatric individuals. A multiplatform metabolomics approach was used to assess the metabolome of plasma samples from a population of children and adolescents with SCA with and without HC treatment along with non‐SCA individuals. Fifty‐three metabolites were identified by ultra‐high performance liquid chromatography coupled to high‐resolution mass spectrometry (UHPLC‐HRMS) and 1H nuclear magnetic resonance (NMR) with a predominance of membrane lipids, amino acids and organic acids. The partial least‐squares discriminant analysis (PLS‐DA) analysis allowed a clear discrimination between the different studied groups, revealing clear effects of the HC treatment in the patients’ metabolome including rescue of specific metabolites to control levels. Increased creatine/creatinine levels under HC treatment suggests a possible increase in the arginine pool and increased NO synthesis, supporting existing models for HC action in SCA. The metabolomics results extend the current knowledge on the models for SCA pathophysiology including impairment of Lands’ cycle and increased synthesis of sphingosine 1‐phosphate. Putative novel biomarkers are suggested.

show abstract

“…This effect is exaggerated by ADMA, which originates from protein and tissue hydrolysis and acts as a strong competitive inhibitor of NO synthases. In fact, increased ADMA concentration in blood has been positively related to fatal outcomes in sickle cell disease [8,11]. Taken as a whole, the alteration of arginine and NO metabolism is an important feature of sickle cell disease that likely explains the observed changes in amino acid content.…”

Section: Plasmatic Metabolic Signaturementioning

confidence: 99%

“…Their initial study revealed 251 significantly altered metabolites, involving glycolysis, pentose phosphate, amino acids, nucleotides, xenobiotics, lipids, fatty acids, and carbohydrate pathways. Lastly, a metabolomic approach was applied in the plasma of patients (n = 23) with sickle cell disease according to their level of albuminuria [8]. The concentration of six metabolites was found to be altered according to albuminuria: betaine, proline, dimethylarginine, glutamate, leucine, and lysine.…”

Section: Introductionmentioning

confidence: 99%

Sickle Cell Disease: Metabolomic Profiles of Vaso-Occlusive Crisis in Plasma and Erythrocytes

Dembélé

Veyrat-Durebex

Guindo

et al. 2020

JCM

View full text Add to dashboard Cite

The metabolomic profile of vaso-occlusive crisis, compared to the basal state of sickle cell disease, has never been reported to our knowledge. Using a standardized targeted metabolomic approach, performed on plasma and erythrocyte fractions, we compared these two states of the disease in the same group of 40 patients. Among the 188 metabolites analyzed, 153 were accurately measured in plasma and 143 in red blood cells. Supervised paired partial least squares discriminant analysis (pPLS-DA) showed good predictive performance for test sets with median area under the receiver operating characteristic (AUROC) curves of 99% and mean p-values of 0.0005 and 0.0002 in plasma and erythrocytes, respectively. A total of 63 metabolites allowed discrimination between the two groups in the plasma, whereas 61 allowed discrimination in the erythrocytes. Overall, this signature points to altered arginine and nitric oxide metabolism, pain pathophysiology, hypoxia and energetic crisis, and membrane remodeling of red blood cells. It also revealed the alteration of metabolite concentrations that had not been previously associated with sickle cell disease. Our results demonstrate that the vaso-occlusive crisis has a specific metabolomic signature, distinct from that observed at steady state, which may be potentially helpful for finding predictive biomarkers for this acute life-threatening episode.

show abstract

Plasma metabolomics analysis in sickle cell disease patients with albuminuria – an exploratory study

Cited by 9 publications

References 10 publications

Metabolomic Profiling of Plasma and Erythrocytes in Sickle Mice Points to Altered Nociceptive Pathways

Metabolomic Profiling of Plasma and Erythrocytes in Sickle Mice Points to Altered Nociceptive Pathways

Blood plasma metabolomics of children and adolescents with sickle cell anaemia treated with hydroxycarbamide: a new tool for uncovering biochemical alterations

Sickle Cell Disease: Metabolomic Profiles of Vaso-Occlusive Crisis in Plasma and Erythrocytes

Contact Info

Product

Resources

About