İnflamasyon İle İlişkili Nöromüsküler Hastalıklarda Dolaşımdaki Mitokondriyal DNA'nın Araştırılması

Abstract

Neuromuscular diseases, mostly being among the rare genetic diseases, include a wide range of syndromes and diseases in which directly or indirectly skeletal muscle structure and function are affected. Recent scientific research has focused on defining common mechanisms involved in the pathogenesis of rare diseases and identifying novel therapeutic targets. Inflammation is one of the prominent features of the majority of neuromuscular diseases. The research carried out on different diseases showed that circulating cell free mtDNA (ccf-mtDNA) takes part in the development of innate immune response as a pro-inflammatory factor. No studies to date have investigated the presence, amount and the potential function of ccf-mtDNA during inflammation process in the inflammatory neuromuscular diseases. In this thesis; absolute quantitation of the amount of ccf-mtDNA found in plasma of patients with (1) autoimmune neuromuscular diseases, (2) the hereditary neuromuscular diseases associated with muscle inflammation and (3) the hereditary neuromuscular diseases without muscle inflammation, was done by RT-qPCR and the results were analyzed in comparison with the healthy control samples. In MG, which is an autoimmune neuromuscular disease, a statistically significant increase in the copy number of ccf-mtDNA by 5,6 fold (p=0,0119) were detected in the patients without any additional treatment compared to control, while there was a statistically significant 1,8 fold (p=0,0476) decrease in the copy number of ccf-mtDNA of the patients who received treatment compared to control. In the second group, there was no statistically significant difference in the ccf-mtDNA copy number in FSHD and LGMD2B patients, while in the third group, there was a statistically significant 2-fold increase (p=0,0017) in SMA patients.

Key words: absolute quantitation, ccf-mtDNA, inflammation, neuromuscular diseases.