New Biomarkers for Neuromuscular Function and Myasthenia Gravis

Sammanfattning: Myasthenia gravis (MG) is an autoimmune disorder, which is caused by autoantibodies against the acetylcholine receptor (AChR). The cardinal symptom is muscle fatigue, which can range from slight weakness of the extraocular muscles (causing droopy eyelids or double vision), to paralysis of the respiratory muscles. Antibodies towards other muscle proteins have been discovered, and MG is now considered a very heterogeneous disease with several subgroups. The severity of symptoms in MG patients is often fluctuating, and the antibody titers do not correlate with disease severity or treatment response. Therefore, there is a great need for reliable biomarkers in MG, both for assessing neuromuscular function, but also for clinical aspects such as disease progression and subgrouping.In Study I, the use of compound motor action potential (CMAP) as a biomarker for muscle status was examined in trained and untrained individuals. We found that trained individuals have a higher CMAP in proximal muscles, and the CMAP value in the biceps correlate with muscle strength in these individuals, indicating that CMAP can be used as a biomarker for muscle function. In Study II, subjects from study I were examined with ultrasound to assess the effect of high-resistance strength training (HRST) on peripheral nerves, and to compare muscle thickness. We did not find a difference in nerve cross-sectional area between the two groups. Trained individuals had thicker biceps muscles. The results from study I and II has led to CMAP and ultrasound being used to evaluate the result of physical exercise as an intervention in MG patients.In Study III, the expression of inflammatory proteins in the sera of MG patients was compared to healthy controls, in search for possible biomarkers. We found eleven proteins to be elevated, which provide new insight to the inflammatory response in MG and have possible functions as new biomarkers of inflammatory activity.In Study IV, the effect of thymectomy on the potential microRNA MG biomarkers miR-150-5p and miR-21-5p was examined. A decrease in miR-150-5p was seen 24 months after thymectomy, which further validate the use of miR-150-5p as a disease-specific biomarker for clinical outcome in AChR positive MG patients.