Expression of aquaporin-4 in thymus and thymoma of myasthenia gravis patients: a pilot study

Abstract

Introduction: Neuromyelitis optica (NMO) is a serious central nervous system disorder characterised by monophasic or recurrent optic neuritis and acute transverse myelitis. 60 to 70% of NMO patients have detectable serum anti-aquaporin-4 (AQP4) antibodies. An autoimmune pathogenesis of NMO is suggested by clinical association of NMO with other autoimmune diseases especially myasthenia gravis (MG). Thymic abnormalities (hyperplasia and thymoma) are common in MG. The role of the thymus and thymoma in the pathogenesis of NMO is unknown. We aimed to study the expression of AQP4 in thymus and thymoma of MG patients. Methods: Thymus and thymoma tissues were obtained from MG patients who underwent thymectomy as standardised treatment. AQP4 protein and mRNA in thymus and thymoma tissues were studied by western blot and reverse transcriptase PCR (RT-PCR). Positive control was human skeletal muscle (express AQP4); negative control was cultured human neuroblastoma cells (do not express AQP4). Results: Four MG patients were studied. Thymoma (two encapsulated, one invading surrounding tissues) from three MG patients (two females; mean age, 37.3 years; range, 22-50 years) express AQP4 detected on western blot; one of the three had RT-PCR performed and was positive for AQP4 mRNA. A single female patient aged 28 years had MG associated with thymic follicular hyperplasia, whose thymus lysate was negative for APQ4 on western blot. All four MG patients were seropositive for anti-acetylcholine receptor antibodies, and none was seropositive for anti-AQP4 antibodies. Conclusion: This pilot study revealed that thymomas of MG patients express AQP4 whereas hyperplastic thymus of MG patients does not express AQP4.