Study On Clinical Characteristics And Biomarkers Of Myasthenia Gravis With MuSK Antibody Positivity

Background Myasthenia gravis(MG)is a chronic autoimmune disease involving the postsynaptic membrane at the neuromuscular junction.Acetylcholine receptor antibody(AchR-Ab)is positive in the vast majority of patients.The clinical manifestations are skeletal muscle weakness or fatigue after exercise,and cholinesterase inhibitors are effective for symptomatic treatment.However,there are still 10%to 15%of patients with negative AchR-Ab in serum.In 2001,a new serum antibody,muscle-specific receptor tyrosine kinase antibody(MuSK-Ab),was found.It was reported that this antibody could be detected in the serum of general MG patients with AchR-Ab negative.The methodology of MuSK-Ab detection is not yet mature,which leads to the delay of the first diagnosis in our country.MuSK-MG still needs clinical research and molecular biology research.Objective 1.A clinical study of MuSK-MG was accomplished,which is based on a radioimmunoprecipitation method for detecting MuSK-Ab in serum.2 Screening microRNA molecules specifically expressed by MuSK-MG,exploring the internal mechanism of the disease by bioinformatics algorithms,and looking for the relationship between microRNA and clinical indicators.Content Method MuSK-Ab was detected by Radioimmunoprecipitation(RIA).The clinical and electrophysiological characteristics of MuSK-MG were analyzed by a case-control studie.A prospective cohort study was conducted to summarize the long-term clinical outcome and prognostic factors of MuSK-MG.The microRNAs,specifically expressed by MuSK-MG was found by the Next Generation Sequencing(NGS),and the validated by RT-qPCR.Result MuSK-MG accounted for 2.27%of all MG,15%of AchR-Ab-negative MG,with a majority of females The median age of onset was 45 years old.There was no significant correlation between the titer of MuSK antibody and the severity of the disease.MuSK-MG mostly starts with eye symptoms(ptosis and diplopia),followed by bulbar symptoms(ambiguous articulation and dysphagia).MGFA is mostly ?b+?b.The overall Repetitive Nerve Stimulation(RNS)positive rate of MuSK-MG(83.3%)was lower than that of general AchR-MG(100%)Within 0.5 to 2 years after onset(median 1.5 years),9 of the 17 patients experienced recurrence.All patients were treated with glucocorticoids or corticosteroids combined with immunosuppressants,and all patients achieved significant improvement in clinical scores(?QMG?3).In our study,the combination of immunosuppressants did not reduce the standardized daily dose of corticosteroids.The expression of miR-340-5p,miR-542-3p,miR-15a-3p,miR-27a-3p in peripheral blood mononuclear cells of MuSK-MG was down-regulated,but there was no significant correlation between the above-mentioned molecules and the titer of MuSK antibody and the severity of the disease.Conclusion 1.MuSK-Ab accounted for 2.27%of totoal MG.Masseter muscle,tongue muscle,bulbar muscle weakness and muscle atrophy are common manifestations of MuSK-MG.MuSK-MG overreacts to cholinesterase inhibitors.2.Long-term glucocorticoid and corticosteroid combined with immunosuppressive therapy can improve the symptoms of MuSK-MG and reduce the titer of MuSK-Ab.Combination of immunosuppressant drugs failed to reduce the dose of glucocorticoid.3.MiR-340-5p,miR-106b-5p,miR-27a-3p and miR-15a-3p are down-regulated by MuSK-MG.These moleculars have potential to become new biomarkers.