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Fudan University Found that Exosome miR-150 is a Potential Biomarker of Myasthenia Gravis Disease
Source: | Author:medical-447 | Published time: 1613 days ago | 87 Views | Share:
Myasthenia gravis (MG) is an autoimmune disease caused by the dysfunction of nerve-muscle junction transmission. The clinical manifestations are mainly partial or systemic skeletal muscle weakness and fatigue. The prevalence rate is (77~150)/1 million, and the annual incidence rate is (4~11)/1 million. Recently, research from Zhao Chongbo and Luo Sushan’s team in Huashan Hospital of Fudan University found out that low-dose rituximab (RTX) is effective in the treatment of patients with acetylcholine receptor (AChR) positive refractory myasthenia gravis. Meanwhile, RTX can reduce the level of serum exosome miR-150. The results suggest that exosome miR-150 is a potential biomarker for myasthenia gravis disease.

Research background:

Myasthenia gravis (MG) is an autoimmune disease that can be alleviated by long-term immunosuppressive therapy in most patients. However, 10%–20% of MG patients did not respond well to conventional treatment methods (including acetylcholinesterase inhibitors, glucocorticoids, common non-steroidal immunosuppressants and thymectomy). These people are known as "refractory" patients. Refractory MG mostly occurs in thymoma-associated patients with AChR + MG, and patients with muscle-specific tyrosine kinase-positive MG (MuSK+), especially female patients, and develop at a younger age.

Rituximab (RTX) of monoclonal antibody targeting B lymphocyte membrane protein CD20 was performed well in patients with refractory MG. However, its effective treatment and immunological mechanism are still under investigation. At present, RTX treatment for refractory MG is characterized by high-dose administration mode similar to that for rheumatic diseases. In addition, RTX may deplete CD20+ T cells, complicating these mechanisms. Therefore, other mechanisms may contribute to RTX’s effectiveness in treating this population.


Clinical issues:

In MG patients, certain stimuli may lead to abnormal expression of some miRNA (miR-150-5p和miR-146a-5p) that may abnormally regulate certain genes in immune cells. However, no studies have determined whether RTX can alter miRNA expression in MG patients. Considering that exosomal miRNA are usually used in the circulating form of biomarkers, the team at Huashan Hospital of Fudan University conducted this prospective, self-disciplined and experimental clinical trial. They investigate whether low dose of RTX (600 mg/6 months) can affect serum exosome levels of miR-150-5p and miR-146a-5p in patients with AChR positive refractory MG.

 

Research results:

In this study, we found that for patients with acetylcholine receptor-positive refractory myasthenia gravis (MG), 6 months after low-dose rituximab (RTX) treatment, RTX reduced the expression of serum exosome miR-150-5p, reduced the three clinical indicators (MGFA, MMT, ADL) of patients and reduced the demand for prednisone of patients. In addition, CD19 + and CD27 + B cells were reduced, suggesting a close association with miR-150-5p. In conclusion, low dose RTX is effective in the treatment of AChR positive refractory MG. In addition, the experimental data provided evidence for miR-150-5p as a potential biomarker for MG.