Circulating cell-free mitochondrial DNA and inflammation in Charcot-Marie-Tooth 1A and Charcot-Marie-Tooth 2A

Circulating cell-free mitochondrial DNA (ccf-mtDNA) is released from cells during such processes as mitophagy and apoptosis and can act as an endogenous damage-associated molecular pattern that activates innate immune responses. We investigated levels of circulating cell-free DNA (ccf-DNA), including ccf-mtDNA and circulating cell-free nuclear DNA (ccf-nDNA), and serum interleukin-1β (IL-1β) in patients with Charcot-Marie-Tooth (CMT) disease, specifically with CMT1A and CMT2A.

This study enrolled 51 patients with CMT disease (42 with CMT1A and 9 with CMT2A, 31 males and 20 females) and 13 healthy controls (6 males and 7 females). The numbers of copies of serum ccf-mtDNA and ccf-nDNA, were quantified using ND1 and ACTB, respectively, before being measured via quantitative real-time polymerase chain reaction. Serum IL-1β levels were measured using enzyme-linked immunosorbent assay. The number of ccf-DNA copies, ND1/ACTB ratio, and IL-1β levels were compared between the three groups. And the correlation analysis was performed.

Serum ND1 levels were higher in patients with CMT1A (p < 0.01) and CMT2A (p < 0.001) than in healthy controls, so was the ND1/ACTB ratio in the CMT1A (p < 0.001) and CMT2A (p < 0.05) groups. Serum IL-1β levels were higher in patients with CMT1A (p < 0.01) and CMT2A (p < 0.001) than in healthy controls. The ND1/ACTB ratio was positively related to the number of onion bulbs in CMT2A. No significant differences in serum ACTB, ND1, ND1/ACTB, or IL-1β levels were observed between the CMT1A and CMT2A groups.

Patients with CMT1A and CMT2A had higher levels of serum ccf-mtDNA and IL-1β than in healthy controls. These findings suggest association between increased circulating mitochondrial DNA and inflammation in CMT disease. However, no subtype-specific differences were identified between CMT1A and CMT2A.