From the Guidelines
Myasthenia gravis is primarily predisposed by autoimmune factors, with antibodies targeting acetylcholine receptors at neuromuscular junctions, and patients are at risk for having or developing a thymoma, as indicated by the most recent study 1. The condition occurs in adults without geographic or racial predilection, although it can also occur in children in different forms, such as transient neonatal myasthenia, congenital myasthenia, and juvenile autoimmune myasthenia 1. Key factors that predispose to myasthenia gravis include:
- Autoimmune factors, with antibodies targeting acetylcholine receptors at neuromuscular junctions, found in nearly all patients with generalized myasthenia and in 40% to 77% of patients with ocular myasthenia 1
- Thymus abnormalities, with patients being at risk for having or developing a thymoma, and thymectomy being indicated in certain cases, such as the presence of thymoma or specific age-based and immune-based characteristics 1
- Genetic factors, although not explicitly mentioned in the most recent study 1, other studies suggest that genetic factors, particularly HLA-B8 and DR3 haplotypes, may play a significant role in increasing susceptibility
- Other autoimmune conditions, infections, certain medications, stress, and fatigue, which can trigger or worsen symptoms, although not directly mentioned in the most recent study 1, are relevant considerations in the context of real-life clinical medicine.
From the Research
Predisposing Factors for Myasthenia Gravis
Several factors have been identified as predisposing individuals to myasthenia gravis (MG), including:
- Genetic factors, particularly those related to the HLA system 2, 3
- Autoantibodies against the acetylcholine receptor (AChR), muscle-specific kinase (MuSK), or other AChR-related proteins 4, 5
- Thymus pathology, including thymic hyperplasia and thymomas 6, 4
- Non-HLA genes, such as PTPN22 and CTLA-4, which have been associated with MG susceptibility 3
Genetic Predisposition
The genetic predisposition to MG is complex and involves multiple factors, including:
- HLA alleles, which have been strongly associated with MG 2, 3
- Non-HLA genes, which have been identified as risk or protective loci for MG 3
- Genome-wide association studies (GWAS), which have identified novel risk loci for MG 3
Autoantibodies and MG
Autoantibodies play a key role in the pathogenesis of MG, with most patients having autoantibodies against the AChR 4, 5. Other autoantibodies, such as those against MuSK, Lrp4, and agrin, have also been identified in MG patients 5. These autoantibodies disrupt cholinergic transmission between nerve terminals and muscle fibers, leading to the clinical manifestations of MG 5.