Muscle-Specific Kinase Myasthenia Gravis

Abstract

Thirty to fifty percent of patients with acetylcholine receptor (AChR) antibody (Ab)negative myasthenia gravis (MG) have Abs to muscle specific kinase (MuSK) and are referred to as having MuSK-MG. MuSK is a 100 kD single-pass post-synaptic transmembrane receptor tyrosine kinase crucial to the development and maintenance of the neuromuscular junction. The Abs in MuSK-MG are predominantly of the IgG4 immunoglobulin subclass. MuSK-MG differs from AChR-MG, in exhibiting more focal muscle involvement, including neck, shoulder, facial and bulbar-innervated muscles, as well as wasting of the involved muscles. MuSK-MG is highly associated with the HLA DR14-DQ5 haplotype and occurs predominantly in females with onset in the fourth decade of life. Some of the standard treatments of AChR-MG have been found to have limited effectiveness in MuSK-MG, including thymectomy and cholinesterase inhibitors. Therefore, current treatment involves immunosuppression, primarily by corticosteroids. In addition, patients respond especially well to B cell depletion agents, e.g., rituximab, with long-term remissions. Future treatments will likely derive from the ongoing analysis of the pathogenic mechanisms underlying this disease, including histologic and physiologic studies of the neuromuscular junction in patients as well as information derived from the development and study of animal models of the disease.

IgG4 Autoantibodies in Organ-Specific Autoimmunopathies: Reviewing Class Switching, Antibody-Producing Cells, and Specific Immunotherapies

“…Unfortunately, to date, there are almost no disease-specific therapies for neuroimmunological diseases. However, in vitro (cell cultures) and in vivo (animal, brain pathology and clinical) studies have suggested the presence of different pathophysiological mechanisms in patients with different antibody types and subtypes ( 152 , 153 ). These findings suggest that special treatment requirements may apply to neuroimmunological diseases with different antibody subtypes, including patients with dominant IgG4 antibodies, and indeed IgG4-AID have a unique response pattern to conventional therapies for autoimmune diseases.…”

Immunopathology of Autoimmune Myasthenia Gravis: Implications for Improved Testing Algorithms and Treatment Strategies

“…Antibody testing has a crucial role for clinical diagnosis confirmation and treatment. Majority of MG patients (around 80–85%) develop Abs against the acetylcholine receptors (AChR; AChR MG), whereas muscle-specific kinase Abs (MuSK; MuSK MG) are detected in 1–10% patients, depending on detection techniques used and the differences between the source population ( 5 , 8 , 9 ). Interestingly, Abs are not detected in around 1–15% of MG patients [that is, negative for AChR, and MuSK Abs with current gold standard methods; seronegative MG (SNMG)] ( 4 , 5 ).…”

Towards Personalized Medicine in Myasthenia Gravis: Role of Circulating microRNAs miR-30e-5p, miR-150-5p and miR-21-5p

“…Different MG subgroups have been proposed based on the age of onset [early onset MG (EOMG; onset ≤ 50 years of age); late onset MG (LOMG; onset > 50 years of age)], antibody profile [acetylcholine receptor antibody seropositive (AChR+), muscle specific tyrosine kinase antibody seropositive (MuSK+)], weakness distribution (OMG vs. GMG) and thymic abnormalities [ 1 , 2 ]. Different subgroups reflect important implications in both prognosis and therapeutic management [ 1 , 3 , 4 ].…”