Determination of lipid metabolism alterations and their association with disease pathogenesis in sickle cell disease

Sickle cell disease (SCD) is a hemoglobinopathy that causes severe anemia and is characterized by lipid abnormalities, oxidative stress and chronic inflammation. It is caused by a single point-mutation in the beta globin gene. Even though the biochemical disease pathophysiology was established more than half a century ago, there are still many questions surrounding the influence of these basic changes on various characteristics seen in patients. We measured parameters associated with lipid profile / lipid metabolism alterations, oxidative stress and chronic inflammation in pediatric patients with SCD and aimed to determine the relationships between these markers, and to assess whether various bioactive lipids (sphingosine 1-phosphate, oxysterols and ceramides) were associated with disease characteristics. The results of our study showed significant associations between anemia-related parameters, oxidative stress, inflammation and lipid profile. When the changes in lipid metabolism and some specific markers of oxidative stress and inflammation were assessed in detail, we came upon results that strongly suggested a significant change in the function of the HDL particle in patients, indicating that the unfavorable environment in the circulation could be leading to major HDL dysfunction. Furthermore, oxysterol and ceramide levels were found to be influential on especially hemolysis parameters and the cholesterol levels of patients. The findings of this study, especially those concerning the relationships between lipid metabolism and other parameters, indicate that SCD pathophysiology is remarkably and significantly related to lipid metabolism and bioactive lipids.