Mark Ciardiello

Professor Janet Rinehart-Kim

Biology 294

2 October 2023

“Circulating mitochondrial DNA is a proinflammatory DAMP in sickle cell disease”

            The article describes a study that aimed to further research what effects of sickle cell disease (SCD) exist in the micro world and how these effects become the causes of other bodily issues. The study analyzed a control group with no SCD gene, a group that was a carrier, a group that had sickle cell disease, and a group that had sickle cell disease that was also causing blood blockages to organs, known as VOE. The researchers studied the levels of cell-free mitochondrial DNA and cell-free nuclear DNA, cf-mtDNA and cfDNA respectively, in the blood of all groups. What the researchers found was that both levels were elevated in patients with SCD. The reasoning behind this was that sickle cells do not mature correctly, which negatively affects how the cells retain their mitochondria. When the cells do not mature properly, the mitochondria cannot fit inside the cell properly and will result in a broken-down mitochondria with broken mitochondrial DNA that ends up as cf-mtDNA. Cf-mtDNA has been shown to increase the formation of NETs, known as neutrophil extracellular traps, which contribute to the inflammation seen in SCD patients. The workings behind the formation of NETs are the result of cf-mtDNA being a damage associated molecule pattern (DAMP) that acts as an alert factor for the immune system to respond to the situation. Due to the situation in SCD patients not involving a pathogen, but rather a genetic condition, the inflammation generated from the immune response is severely negative and can result in pain for the patient.

References

Tumburu L, et al. Circulating mitochondrial DNA is a proinflammatory DAMP in sickle cell disease. Blood 137, 3116-3126 (2021).