In a recent study of patients with beta-thalassemia, researchers characterized changes to the lipid content of red blood cell (RBC) membranes following treatment with hydroxyurea. They reported their findings in the journal Molecular Omics.
A key feature the researchers evaluated was the effect of IVS mutations in patients. IVS mutations, particularly in IVS 1-5 and marked by a change from guanine to cytosine (G>C), are associated with beta-thalassemia, the researchers explained in their report. Additionally, in beta-thalassemia , the membrane integrity of RBCs is compromised, and lipids are critical components for membrane structure. The researchers designed the study to examine differences in the lipid components of RBCs in patients with beta-thalassemia based on treatment and IVS mutational status.
RBCs were collected from patients with b-thalassemia, and the RBC lipidome was isolated. Lipid profiles were examined using liquid chromatography/tandem mass spectrometry. The researchers evaluated data regarding lipid profiles in the context of the presence or absence of hydroxyurea treatment and whether an IVS mutation was present or not.
The study included 50 patients, with 3 patients under 2 years of age, 35 patients from 2 to 9 years of age, and 12 patients above 9 years of age. There were 36 patients with IVS mutations, of whom 22 were treated with hydroxyurea and 14 were not. There were 14 patients without IVS mutations, of whom 10 were treated with hydroxyurea and 4 were not.
Patient subgroups revealed many potential differences in the abundance of lipid species. The presence of an IVS mutation appeared associated with trends of different expression levels for multiple lipid species, relative to the lipid signatures of patients without IVS mutations.
In patients with and without IVS mutations, treatment with hydroxyurea was associated with increases in complex membrane lipids, including phospholipids and glycerides, and generally with downregulation of fatty acids. However, the opposite patterns were reportedly seen in lipid profiles of patients with IVS mutations who lacked treatment with hydroxyurea. The researchers noted that fatty acids are linked to the degradation of complex lipids.
The researchers concluded that IVS mutations appeared associated with a poorer RBC membrane lipid profile with beta-thalassemia. Additionally, the researchers considered the results to indicate that hydroxyurea treatment was linked to improved lipid profiles with beta-thalassemia, both with and without IVS mutations.
“The study will lead to an understanding of the disorder at the molecular level, eventually initiating improved treatment options and identifying the phenotype of the patients,” the researchers wrote in their report.
Khan MBN, Iftikhar F, Khan T, et al. IVS I-5 (G > C) is associated with changes to the RBC membrane lipidome in response to hydroxyurea treatment in b-thalassemia patients. Mol Omics. Published online May 17, 2022. doi:10.1039/d2mo00008c