This paper reviews the recent advances in the field of MG which span from autoantibody profiling and pathogenic mechanisms to therapy innovation. The overview is highlighting specifically the data and the needs of targeted treatments in the light of precision medicine in MG.
MG is an antibody-mediated autoimmune disorder that targets the neuromuscular junction (NMJ), resulting in fluctuating fatigable muscle weakness that typically presents initially with ocular symptoms but frequently generalizes to encompass bulbar, respiratory, and limb girdle functions. In the past half century, improvements in accurate and prompt diagnosis and treatment have simultaneously increased the estimated prevalence of MG and improved the prognosis for patients, leading to a substantial reduction in mortality attributable to MG. Among patients with an MG diagnosis, MG-attributable mortality was reduced from 70% in the 1930s to 30% by 1955, and is now well under 10%. During the same period, the estimated prevalence of MG increased more than 10-fold, from 1 per 200,000 to 1 per 17,000. In the last years improvements in treatment strategies and the prognosis of MG have been relatively broad-based, with the treatment goal of establishing complete stable remission (CSR). However, recent work has demonstrated heterogeneity in disease course and treatment response based on patient antibody profile: patients with antibodies to muscle-specific tyrosine kinase (anti–MuSKpositive) appear to be less responsive to conventional treatment than those with antibodies to the acetylcholine receptor (anti–AChR-positive) or those without anti-MuSK or anti-AChR antibodies.
Novel data from recent studies on immune-pathogenesis increased substantially our knowledge on the disease. The use of cell-based assays has greatly improved autoantibody detection in MG patients, and the mechanisms of action of these antibodies have been described. The role of Toll-like receptor activation in the generation of thymic alterations and anti-acetylcholine receptor autosensitization has been further investigated implementing our understanding on the relationships between innate immunity and autoimmunity. Additional studies have been focused on the alterations of T/B-cell regulatory mechanisms in thymus and peripheral blood of MG patients. microRNAs and genetic factors are also emerging as key biomarkers in MG pathogenesis and prediction of drug efficacy in individual patients.
The recent immune and pathological findings in MG promise to improve MG treatment, via the development of more precise and personalized therapies.
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