The Thymus In Myasthenia Gravis

Thymic abnormalities are clearly associated with myasthenia gravis but the nature of the association is uncertain. Ten percent of patients with myasthenia gravis have a thymic tumor and 70% have hyperplastic changes (germinal centers) that indicate an active immune response. These are areas within lymphoid tissue where B-cells interact with helper T-cells to produce antibodies. Because the thymus is the central organ for immunological self-tolerance, it is reasonable to suspect that thymic abnormalities cause the breakdown in tolerance that causes an immune-mediated attack on AChR in myasthenia gravis. The thymus contains all the necessary elements for the pathogenesis of myasthenia gravis: myoid cells that express the AChR antigen, antigen presenting cells, and immunocompetent T-cells. Thymus tissue from patients with myasthenia gravis produces AChR antibodies when implanted into immunodeficient mice. However, it is still uncertain whether the role of the thymus in the pathogenesis of myasthenia gravis is primary or secondary. Most thymic tumors in patients with myasthenia gravis are benign, well-differentiated and encapsulated, and can be removed completely at surgery. It is unlikely that thymomas result from chronic thymic hyperactivity because myasthenia gravis can develop years after thymoma removal and the HLA haplotypes that predominate in patients with thymic hyperplasia are different from those with thymomas. Patients with thymoma usually have more severe disease, higher levels of AChR antibodies, and more severe EMG abnormalities than patients without thymoma. Almost 20% of patients with myasthenia gravis whose symptoms began between the ages of 30 and 60 years have thymoma; the frequency is much lower when symptom onset is after age 60.