Metabolomic profiling for dyslipidemia in pediatric patients with sickle cell disease, on behalf of the IHCC consortium

Abstract

Background Previous study has shown that dyslipidemia is common in patients with Sickle cell disease (SCD) and is associated with more serious SCD complications. Methods This study investigated systematically dyslipidemia in SCD using a state-of-art nuclear magnetic resonance (NMR) metabolomics platform, including 147 pediatric cases with SCD and 1234 controls without SCD. We examined 249 metabolomic biomarkers, including 98 biomarkers for lipoprotein subclasses, 70 biomarkers for relative lipoprotein lipid concentrations, plus biomarkers for fatty acids and phospholipids. Results Specific patterns of hypolipoproteinemia and hypocholesterolemia in pediatric SCD were observed in lipoprotein subclasses other than larger VLDL subclasses. Triglycerides are not significantly changed in SCD, except increased relative concentrations in lipoprotein subclasses. Decreased plasma FFAs (including total-FA, SFA, PUFA, Omega-6, and linoleic acid) and decreased plasma phospholipids were observed in SCD. Conclusion This study scrutinized, for the first time, lipoprotein subclasses in pediatric patients with SCD, and identified SCD-specific dyslipidemia from altered lipoprotein metabolism. The findings of this study depict a broad panorama of lipid metabolism and nutrition in SCD, suggesting the potential of specific dietary supplementation of the deficient nutrients for the management of SCD.

Metabolic signatures of cardiorenal dysfunction in plasma from sickle cell patients as a function of therapeutic transfusion and hydroxyurea treatment

“…61 Here we performed network analyses of combined metabolomics and clinical data, which showed a strong association between hematological (e.g., HbS%) and clinical parameters with all metabolites mentioned in this discussion, as well as free fatty acids and acyl-carnitines. Of note, elevated kynurenine levels had been previously associated with increased susceptibility to hemolysis in the context of obesity, 62 whereby depletion in circulating free fatty acids (previously also reported in pediatric patients with SCD 63 ) and elevation acyl-carnitines had been identified as a marker of increased membrane RBC lipid damage and remodeling. This observation was in keeping with previous reports on the activation of the so-called Lands cycle in the context of SCD 64 (or even just sickle cell trait), 65 or other osmotic, mechanical or oxidative stressors to RBC, such as blood storage, 66 exercise, 67 chronic 68 or acute kidney dysfunction.…”

Metabolic signatures of cardiorenal dysfunction in plasma from sickle cell patients, as a function of therapeutic transfusion and hydroxyurea treatment

“…61 Here we performed network analyses of combined metabolomics and clinical data, which showed a strong association between hematological (e.g., HbS%) and clinical parameters with all metabolites mentioned in this discussion, as well as free fatty acids and acyl-carnitines. Of note, elevated kynurenine levels had been previously associated with increased susceptibility to hemolysis in the context of obesity, 62 whereby depletion in circulating free fatty acids (previously also reported in pediatric patients with SCD 63 ) and elevation acyl-carnitines had been identified as a marker of increased membrane RBC lipid damage and remodeling. This observation was in keeping with previous reports on the activation of the so-called Lands cycle in the context of SCD 64 (or even just sickle cell trait) 65 , or other osmotic, mechanical or oxidative stressors to RBCs, such as blood storage, 66 exercise, 67 chronic 68 or acute kidney dysfunction.…”