Abstract
BackgroundMyasthenia gravis is a disorder of neuromuscular transmission associated with autoantibodies against the nicotinic acetylcholine receptor. We have previously developed a customized protein macroarray comprising 1827 potential human autoantigens, which permitted to discriminate sera of patients with different cancers from sera of healthy controls, but has not yet been evaluated in antibody-mediated autoimmune diseases.ObjectiveTo determine whether autoantibody signatures obtained by protein macroarray separate sera of patients with myasthenia gravis from healthy controls.MethodsSera of patients with acetylcholine receptor antibody-positive myasthenia gravis (n = 25) and healthy controls (n = 32) were analyzed by protein macroarrays comprising 1827 peptide clones.ResultsAutoantibody signatures did not separate patients with myasthenia gravis from controls with sufficient sensitivity, specificity, and accuracy. Intensity values of one antigen (poly A binding protein cytoplasmic 1, p = 0.0045) were higher in patients with myasthenia gravis, but the relevance of this and two further antigens, 40S ribosomal protein S13 (20.8% vs. 0%, p = 0.011) and proteasome subunit alpha type 1 (25% vs. 3.1%, p = 0.035), which were detected more frequently by myasthenia gravis than by control sera, currently remains uncertain.ConclusionSeroreactivity profiles of patients with myasthenia gravis detected by a customized protein macroarray did not allow discrimination from healthy controls, compatible with the notion that the autoantibody response in myasthenia gravis is highly focussed against the acetylcholine receptor.
Highlights
Myasthenia gravis (MG) is an overall rare disorder of neuromuscular transmission, clinically characterized by fluctuating muscle weakness and abnormal fatigability [1]
Seroreactivity profiles of patients with myasthenia gravis detected by a customized protein macroarray did not allow discrimination from healthy controls, compatible with the notion that the autoantibody response in myasthenia gravis is highly focussed against the acetylcholine receptor
Autoantibody profiles did not discriminate patients with MG from healthy controls with acceptable sensitivity, specificity, and accuracy, compatible with the notion that the autoantibody response in myasthenia gravis is highly focussed against the acetylcholine receptor
Summary
Myasthenia gravis (MG) is an overall rare disorder of neuromuscular transmission, clinically characterized by fluctuating muscle weakness and abnormal fatigability [1]. Weakness is caused by T-helper cell dependent autoantibodies against the nicotinic acetylcholine receptor (AChR antibodies), which can be detected in approximately 80–90% of patients with generalized MG [1,2,3,4]. Serum autoantibodies against a number of different antigens have been reported in patients with MG [5]. Among these are antibodies against myosin [6], filamin, vinculin, and tropomyosin [7], as well as rapsyn [8]. Myasthenia gravis is a disorder of neuromuscular transmission associated with autoantibodies against the nicotinic acetylcholine receptor. We have previously developed a customized protein macroarray comprising 1827 potential human autoantigens, which permitted to discriminate sera of patients with different cancers from sera of healthy controls, but has not yet been evaluated in antibody-mediated autoimmune diseases
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