Plasma miR-150-5p as a biomarker for immunosuppressive therapy response in acetylcholine receptor positive myasthenia gravis: a long-term prospective longitudinal study.

Insufficient effectiveness and adverse effects of immunosuppressive therapy, seen in around 20 % of acetylcholine receptor (AChR) positive myasthenia gravis (MG) patients, highlight the need for new biomarkers. MicroRNAs (miRNAs), small regulatory non-coding RNAs with tissue-specific expression, have emerged as potential biomarkers due to their abundance and accessibility in body fluids. Several miRNAs involved in immune system and drug metabolism have been associated with improvement of neuromuscular status or response to immunosuppressive therapy in AChR-positive MG patients in cross-sectional studies. Here, we explored miRNAs as plasma biomarkers for immunosuppressive therapy response in a prospective longitudinal study of newly diagnosed, drug-naïve patients. Clinical examination and plasma sampling were performed at three time points: baseline (pre-treatment), 6-month, and 12-month follow-ups. MiRNA levels were quantified by qPCR. Three out of eight analyzed miRNAs (miR-150-5p, miR-27a-3p, and miR-21-5p) showed treatment-related changes. Among them, miR-150-5p level was negatively correlated with patient functionality (MG Activities of Daily Living score - MG-ADL; p = 0.007, ρs=-0.433), muscle strength and weakness (Quantitative MG score - QMG; p = 0.002, ρs=-0.355) and overall symptoms (MG Composite score - MGC; p = 7.814e-5, ρs=-0.457). Pre-treatment miR-150-5p levels showed excellent prognostic ability to discriminate responders from not-responders based on achieved minimal clinical expression (AUC=0.85, p = 0.0076) and MG-ADL (AUC=0.86, p = 0.016) at 12-month follow-up. Predictive performance was also acceptable based on QMG and MGC (AUC=0.74, p = 0.001 and AUC=0.73, p = 0.0002, respectively). Our findings imply plasma miR-150-5p as a potential biomarker for predicting immunosuppressive therapy response in AChR-positive MG, suggesting its further investigation for disease monitoring and a personalized medicine approach.