Experimental Autoimmune Myasthenia Research Articles

Autoimmune Channelopathies and Related Neurological Disorders

Ion channels are crucial elements in neuronal signaling and synaptic transmission, and defects in their function are known to underlie rare genetic disorders, including some forms of epilepsy. A second class of channelopathies, characterized by autoantibodies against ligand- and voltage-gated ion channels, cause a variety of defects in peripheral neuromuscular and ganglionic transmission. There is also emerging evidence for autoantibody-mediated mechanisms in subgroups of patients with central nervous system disorders, particularly those involving defects in cognition or sleep and often associated with epilepsy. In all autoimmune channelopathies, the relationship between autoantibody specificity and clinical phenotype is complex. But with this new information, autoimmune channelopathies are detected and treated with increasing success, and future research promises new insights into the mechanisms of dysfunction at neuronal synapses and the determinants of clinical phenotype.

Myasthenia gravis: A survey

Myasthenia gravis is a chronic disease characterized by a fluctuating weakness of voluntary muscle, with a preference for the muscles innervated by cranial nerves. The pathophysiological mechanism is a loss of postsynaptic acetylcholine receptors to less than 20–30% so that the safety margin of neuromuscular transmission is lost. It is probable that the function of the remaining acetylcholine receptors is impaired by antibodies against receptor proteïn, which can be demonstrated in the serum in 80–90% of the patients, and which are highly specific for the disease. An experimental autoimmune myasthenia can be induced in many animal species by immunization with purified receptor proteïn and this disease is remarkably similar to the human myasthenia with exception of the fluctuating course. The human disease has to be considered as an autoimmune disease, although the initiating mechanism is unknown. The occurrence of tumors of the thymus in 10–15% and the presence of germinal centres in about 70% of the thymus glands removed by operation are highly suggestive of the importance of the thymus in the pathogenesis, but the definite mechanism (harbouring of an abnormal antigen in myoid cells, or/and false instruction of thymocytes with lack of suppressor cells) is essentially unknown. In most patients the disease tends to have a favourable course from 5–10 years after onset and complete remissions occur in about 20% after 10–20 years. Therapy with anticholinesterases, providing an increase in acetylcholine, is of partial benefit in most patients. Thymectomy has an excellent effect in about 30% of the patients without thymoma under the age of 40 during the first three years of the disease, and is of benefit in still another 30–40%. The use of prednisone and immuno-suppressive drugs has improved the prognosis of the 20% of the patients with severe life threatening symptoms, half of whom have a thymoma.

Passive transfer of experimental autoimmune myasthenia by lymph node cells in inbred guinea pigs.

Passive transfer of experimental autoimmune myasthenia (EAM) was performed with lymph node cells from donor guinea pigs immunized with purified acetylcholine receptor (AChR) from Torpedo californica. Recipient animals revealed the same clinical signs and electromyographic patterns as observed in actively challenged animals. These phenomena are parallel to the clinical manifestations of the human disease myasthenia gravis, in which cellular response to AChR was recently demonstrated.