Non-motor symptoms in myasthenia gravis: Attributed to T-cell clones from thymoma

Autoimmune myasthenia gravis (MG) comprises a broad spectrum of non-motor symptoms. Patients with MG sometimes have psychiatric symptoms, such as depression and anxiety, which impair their quality of life. However, these symptoms are not principally immune-mediated. Moreover, some patients with MG have additional autoimmune disorders. The clinical manifestations of these diseases are also considered non-motor symptoms, even though the autoimmune mechanisms underlying the association between MG and these disorders are not fully understood. In this review, we clarify that the non-motor symptoms of autoimmune disorders are attributed to abnormal T-cell clones from thymomas. We review the clinical characteristics of patients with MG and associated thymomas who exhibit non-motor symptoms based on previously reported cases and our multicenter cooperative study. CD8⁺ T-cell cytotoxicity against hematopoietic precursor cells in the bone marrow and unidentified autoantigens in hair follicles result in the development of pure red cell aplasia, immunodeficiency, and alopecia areata. In contrast, neuromyotonia, limbic encephalitis, myocarditis, and taste disorders are autoantibody-mediated disorders, as is MG. Autoantibodies to several types of voltage-gated potassium channels and related molecules can evoke various neurological and cardiac disorders. Approximately 25% of patients with MG and associated thymomas experience at least one non-motor symptom. Non-motor symptoms affect many target organs and result in a broad disease spectrum, ranging from the impairment of quality of life to lethal conditions.