Functional mitochondria are retained in red blood cells (RBCs) of patients with sickle cell disease (SCD), possibly causing immune responses and leading to complications, according to an article published in the British Journal of Haematology.

Patients with SCD had a significant increase in mature RBCs (CD71) staining positive for mitochondria (MitoTracker+) than healthy blood donors and people with the sickle cell trait (13.0 ±10.4%; P <.0001). A significant increase in the number of CD71+ reticulocytes staining positive for mitochondria (MitoTracker+) was also observed in SCD patients compared to healthy donors and those with sickle cell trait (82.8 ± 21.8%; P <.001).

Through metabolomic, proteomic, and lipidomic analyses of sorted RBCs from SCD patients, MitoTracker+ mature RBCs and reticulocytes showed active pathways associated with mitochondrial function. Specific examples included carboxylic acid from the TCA cycle, several acyl-carnitines derived from mitochondrial fatty-acid metabolism, polyamines, and several phosphatidylethanolamines, sphingomyelins, and ceramides.

MitoTracker+ RBCs and reticulocytes also had detectable levels of oxidative phosphorylation enzymatic activity and mitochondrial DNA (mtDNA). Components of mitochondrial electron transport chain components, mitochondrial metabolism, glyoxylate and glutathione metabolism, and mitochondrial function were also detected in reticulocytes and MitoTracker+ cells through proteomic analysis.

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“This study provides, for the first time, a comprehensive evaluation of the impact of mitochondria on the metabolism and proteome of mature RBCs in patients with SCD,” the study’s authors said.

In vitro cocultures of opsonized RBCs from patients with SCD combined with primary neutrophils from control subjects induced innate immune responses. Levels of IFNβ were significantly increased in cocultures containing mitochondrial positive RBCs an average 4.9 fold above those lacking mitochondria (P =.05). Relative expression levels of MxA, IFI44, and TNFα in mitochondrial positive RBCs showed increased levels compared to those lacking mitochondria, however, the differences were not significant.

“Furthermore, it demonstrates that RBCs from patients with SCD not only retain mitochondria, but also that these mitochondria remain functional and can induce anti-viral responses upon recognition by immune cells,” the authors wrote.

Reference

Moriconi C, Dzieciatkowska M, Roy M, et al. Retention of functional mitochondria in mature red blood cells from patients with sickle cell disease. Br J Haematol. Published online June 7, 2022. doi:10.1111/bjh.18287