Myasthenia Gravis: Autoantibody Specificities and Their Role in MG Management

Abstract

Myasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction, characterized by skeletal muscle weakness and fatigability. It is caused by autoantibodies targeting proteins of the neuromuscular junction; ~85% of MG patients have autoantibodies against the muscle acetylcholine receptor (AChR-MG), whereas about 5% of MG patients have autoantibodies against the muscle specific kinase (MuSK-MG). In the remaining about 10% of patients no autoantibodies can be found with the classical diagnostics for AChR and MuSK antibodies (seronegative MG, SN-MG). Since serological tests are relatively easy and non-invasive for disease diagnosis, the improvement of methods for the detection of known autoantibodies or the discovery of novel autoantibody specificities to diminish SN-MG and to facilitate differential diagnosis of similar diseases, is crucial. Radioimmunoprecipitation assays (RIPA) are the staple for MG antibody detection, but over the past years, using cell-based assays (CBAs) or improved highly sensitive RIPAs, it has been possible to detect autoantibodies in previously SN-MG patients. This led to the identification of more patients with antibodies to the classical antigens AChR and MuSK and to the third MG autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), while antibodies against other extracellular or intracellular targets, such as agrin, Kv1.4 potassium channels, collagen Q, titin, the ryanodine receptor and cortactin have been found in some MG patients. Since the autoantigen targeted determines in part the clinical manifestations, prognosis and response to treatment, serological tests are not only indispensable for initial diagnosis, but also for monitoring treatment efficacy. Importantly, knowing the autoantibody profile of MG patients could allow for more efficient personalized therapeutic approaches. Significant progress has been made over the past years toward the development of antigen-specific therapies, targeting only the specific immune cells or autoantibodies involved in the autoimmune response. In this review, we will present the progress made toward the development of novel sensitive autoantibody detection assays, the identification of new MG autoantigens, and the implications for improved antigen-specific therapeutics. These advancements increase our understanding of MG pathology and improve patient quality of life by providing faster, more accurate diagnosis and better disease management.

MuSK-antibodies are associated with worse outcome in myasthenic crisis requiring mechanical ventilation

“…Lately more and more studies discuss a potential favorable role of IA in MuSK-MC, as it is an antibody selective plasma exchange therapy with less risk for side effects compared to Plasmapheresis. This could be confirmed by first data from Lazaridis et al [ 14 , 19 ] indicating a significant and sufficient reduction of MuSK-AB serum level through IA. Barth et al [ 12 ], who pointed out an equal effect of PE/IA vs. IVIG, stated that the presence of AChR-ABs predicted a better outcome compared to MuSK-MG or seronegative MG, which might furthermore empower a differentiation of decision-making in MC treatment due to its antibody status.…”

Comorbid Autoimmune Diseases in Patients With Myasthenia Gravis: A Retrospective Cross-Sectional Study of a Chinese Cohort

“…Previous studies have reported a lower percentage of second ADs in thymoma-associated MG than that in non-thymoma-associated MG ( 28 – 30 ). A lower risk for autoimmune comorbidity has also been demonstrated in patients with muscle antibodies against titin and ryanodine receptor, which predicts the presence of thymoma in patients with MG ( 11 , 31 , 32 ). Similarly, we found that the percentage of comorbid ADs in patients with MG with thymoma was lower than that in those without thymoma.…”

Comparative Analysis of BIOCHIP Mosaic-Based Indirect Immunofluorescence with Enzyme-Linked Immunosorbent Assay for Diagnosing Myasthenia Gravis

“…The diagnosis of MG is based on a multistep approach, which combines clinical features and laboratory criteria (Figure 3). The sensitive and specific detection of anti-AChR and anti-MuSK autoantibodies has become an essential laboratory investigation in evaluating patients with MG, because seropositivity has diagnostic, prognostic, and therapeutic implications [15][16][17][18][19]. Recent studies report that anti-MuSK positive patients have a worse prognosis with predominant bulbar and respiratory muscle involvement and frequent respiratory crises [3,[20][21][22].…”