AUTOANTIBODIES IN MYASTHENIA GRAVIS: THE CLINICAL VIEW

Abstract

Myasthenia gravis is an antibody-mediated, autoimmune disorder affecting the postsynaptic membrane of the neuromuscular junction. It is becoming apparent that myasthenia gravis is not a single disease, but is compromised of clinical subtypes that may be distinguished by the age of onset, clinical presentation of the disease, thymic pathology and autoantibody profile. Two-well characterized autoantibodies are known to be specific for, and to play causative role in myasthenia gravis; the anti-AChR and the anti-MuSK auto-antibodies. In the appropriate clinical setting, these antibodies are diagnostic for myasthenia gravis. While very useful for diagnostic purpose, these autoantibodies have questionable utility for disease monitoring with the possible exception of anti-MuSK antibodies. Recent studies have demonstrated the presence of anti-LRP4 Abs in a proportion of AChR and MuSK antibody-negative patients. These antibodies have been reported in generalized but also in ocular cases. Striated muscle (striational) antibodies that recognize muscle cytoplasmic proteins (mostly titin, ryanodine receptor) are found in subtypes of AChR-positive patients. Specifically, they are detected in the majority of thymoma patients irrespective of the age of onset and in about half of late onset patients. So, the detection of anti-titin antibodies can’t discriminate between thymoma and non-thymoma in late onset patients. However, the presence of these antibodies in patients with early onset myasthenia raises the suspicion of a thymoma. When both titin and ryanodine receptor antibodies are present both the sensitivity and the specificity for thymoma in myasthenia are about 70%. The striational antibodies are probably not pathogenic, but their presence is associated with other distinctive clinical features, such as myositis and myocarditis.