Mitochondrial DNA as a danger-associated molecular pattern in Myalgic encephalitis and endometrial cancer

Mitochondria are complex organelles, which are involved in various important metabolic pathways. Due to their proteobacterial evolutionary origin, the mitochondria DNA resemble unmethylated microbial CpG motifs, which possess the ability to interact with pathogen associated DNA sensors, such as TLR9 and activate the NLRP3 inflammasome, inducing pro- inflammatory cytokines. Myalgic encephalitis (ME), also called chronic fatigue syndrome (CFS) is a disease of unknown ethology. A dysfunctional energy production might be a piece of the puzzle, to explain the fatigue. By examine the presence of anti-mitochondrial antibodies (AMA) and anti-cardiolipin antibodies (ACA), as well as evaluating mitochondrial DNA as a danger-associated molecular pattern (DAMP) we aim to provide an important piece of knowledge to further understand the disease. ME patients are at risk of developing B-cell lymphoma. For comparison we have analyzed mtDNA levels in endometrial cancer, which is the most common malignancy of the female genital tract. By measuring both mtDNA and nuclear DNA, our aim was to compare two surgical methods: traditional open abdominal surgery with robot assisted laparoscopic surgery for DAMP-signaling, that is tissue damage and immune activation. We found that neither AMA nor ACA could be detected in ME plasma samples, and the level of circulatory mtDNA did not differ from healthy controls. However, mtDNA levels in cancer patients was significantly increased compared to healthy controls (p<0.0001). No difference in tissue damage and immune activation, as judged from mtDNA and nDNA levels could be identified between the two surgical methods. We conclude that ME patients patient mitochondrial dysfunction cannot be explained by abnormal antibodies or mtDNA. In contrast cancer patients have significantly raised levels of the mtDNA DAMP in circulation.