Red blood cells (RBCs) with sickle structures are sickle cell disease (SCD)-related blood disorders that are more susceptible to hemolysis and can affect the pathophysiology of the disease. Patients with SCD have high rates of alloimmunization, despite RBC transfusions being a possible form of therapy. For a study, researchers postulated that RBCs could produce type 1 interferon from SCD patients because these cells had functionally active mitochondria.

In comparison to healthy blood donors, they examined blood samples from more than 100 patients with SCD and discovered higher frequencies of mitochondria in reticulocytes and mature RBCs. With the use of flow cytometry, electron microscopy, and proteomic analysis, the existence of mitochondria in mature RBCs was established. Enzymatic activity and higher amounts of metabolites produced by the mitochondria demonstrated the metabolic competence of the adult RBCs. RBCs with metabolically active mitochondria could cause more oxidative stress, which might help with or make SCD problems worse. Type 1 interferons, known to raise RBC alloimmunization rates, were produced due to a coculture of neutrophils and RBCs that had mitochondrial markers.

The findings implied improper retention of mitochondria in RBCs might play an unrecognized role in SCD complications and be a risk factor for RBC alloimmunization. They further showed that mitochondria maintained in mature RBCs are functional and can trigger immunological responses.