An update on laboratory diagnosis in myasthenia gravis

Abstract

This review describes the state of the art for the use of laboratory testing in myasthenia gravis. The review brings a detailed description of the different clinical forms of auto-immune myasthenia and of the Lambert Eaton Myasthenic Syndrome (LEMS). The stress the differences between the different forms of acquired (auto-immune) myasthenia. Then they present a summary of the different antibodies found in the disease. They insist on the advantage of the RIPA assay to measure antibodies to the acetylcholine receptor. They stress the different types of contribution of each of these antibodies to the clinical diagnosis. They also describe the methods to measure each of the specific antibodies that have recently permitted to split the diagnosis: Abs to omega-conotoxin receptor in Lambert Eaton Myasthenic Syndrome (LEMS), abs to the acetylcholine receptor (AchR) in MG, Abs to muscle specific tyrosine kinase (MuSK) in Ab negative MG, and Abs to low molecular weight receptor related low-density lipo protein-4 (LRP-4). They also broach over the striated antibodies, less frequent and clinically less useful such as anti-titin, -ryanodine, -agrin and -rapsyn. This represent a 360° view of the field as presented in Toronto in October 2014.

Autoantibodies in acquired myasthenia gravis: Clinical phenotype and immunological correlation

“…2 ELISA technique is fraught with both false negatives (27%) and false positives (5%). 2 Cell-based assays are non-radioactive and have further improved sensitivity and specificity. 4,6,10 Besides, late appearance of AChR antibodies due to low levels or low affinity for the receptor in the initial stages and antibodies to "clustered"…”

“…The AChRs are maintained by a network of proteins: muscle-specific kinase (MUSK), low-density lipoprotein receptor-related protein 4 (LRP4), titin, ryanodine, agrin and rapsyn. [1][2][3] The post-synaptic membrane of the neuromuscular junction is thrown into folds. The AChRs are located on the crests, while the esterases that metabolize acetylcholine are located in the troughs of these folds.…”

“…Thus, the "geographic advantage" offered by the location of AChRs vis-à-vis the esterases is lost. 2 About 60% of subjects with ocular myasthenia and 85% with generalized MG have AChR antibodies. 2 Antibodies against other components of the neuromuscular junction viz MUSK, LRP4, agrin and collagen-Q are also implicated in the pathophysiology of MG. 1 While AChR antibodies are fairly well characterized, knowledge regarding other antibodies is evolving.…”

Immune-Mediated Neurological Disorders

“…Several autoantibodies targeting postsynaptic proteins, including acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), low density lipoprotein receptor-related protein 4 (LRP4), and agrin antibodies, have been identified in the majority of patients with MG [26]. Most patients with LEMS have autoantibodies targeting presynaptic voltage-gated calcium channels [26].…”

“…Several autoantibodies targeting postsynaptic proteins, including acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), low density lipoprotein receptor-related protein 4 (LRP4), and agrin antibodies, have been identified in the majority of patients with MG [26]. Most patients with LEMS have autoantibodies targeting presynaptic voltage-gated calcium channels [26]. Patients with seronegative NMJ disorders could still have underlying immune-mediated neuromuscular transmission defects, but clinicians should also entertain the possibility of hereditary NMJ disorders or congenital myasthenic syndromes.…”