Plasma Biomarkers of Mitochondrial Dysfunction in Patients with Myasthenia Gravis.

Abstract

Background. Myasthenia gravis is an autoimmune neuromuscular disease characterized by fatigue of striated muscles due to impaired neuromuscular transmission. Mitochondrial dysfunction, according to published data, contributes significantly to metabolic abnormalities, oxidative stress and, as a consequence, the persistence of inflammation. MicroRNAs, which are post-transcriptional regulators of expression, are able to contribute to the aberrant functioning of mitochondria. In this study, with the aim of searching for biomarkers at the level of circulating microRNAs and proteins, the expression of three microRNAs was analyzed and the concentration of mitochondrial proteins was measured in the blood plasma of patients with myasthenia gravis (n = 49) in comparison with healthy volunteers (n = 31). Methods. Expression analysis was performed by RT-PCR, mathematical data processing was carried out using the Livak method, and protein concentration was determined by enzyme immunoassay. Results. Our plasma expression analysis revealed a statistically significant increase in hsa-miR-194-5p expression (Log10 Fold Change = 1.46, p-value < 0.0001) and a statistically significant decrease in hsa-miR-148a-3p expression (Log10 Fold Change = -0.65, p-value = 0.02). A statistically significant decrease in plasma COQ10A concentration was also found (0.911 [0.439; 1.608] versus 1.815 [1.033; 2.916] for myasthenia gravis and controls, respectively, p-value = 0.01). Conclusion. Our data suggest hsa-miR-148a-3p and hsa-miR-194-5p, as well as COQ10A, as potential biomarkers of mitochondrial dysfunction in myasthenia gravis.