Myasthenia Gravis: Analysis of Serum Autoantibody Reactivities to 1827 Potential Human Autoantigens by Protein Macroarrays

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.

An Autoantigen Profile from Jurkat T-Lymphoblasts Provides a Molecular Guide for Investigating Autoimmune Sequelae of COVID-19

“…Poly(A)-binding proteins bind the poly(A) tail of messenger RNAs and control mRNA stability and translation initiation. Although PABPC3 has not yet been reported as an autoAg, its paralog PABPC1 has been found to be an autoAg [25].…”

Focal adhesion ribonucleoprotein complex proteins are major humoral cancer antigens and targets in autoimmune diseases

“…We next investigated the common features of the identified protein antigens of the tumor-specific dominant B cell clones. Knowledge-based exploration of the biological and clinical features of the protein antigens revealed that almost all the humoral protein antigens we discovered in tumor environments have also been reported as immunological targets of humoral autoimmunity in multiple autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), myasthenia gravis (MG), multiple sclerosis (MS), primary biliary cirrhosis (PBC), and Sjogren's syndrome (SS) [11][12][13][14][15][16][17][18][19][20][21][22] (Table 1). This shared feature of humoral immunity in tumors and autoimmunity in view of their target protein antigens suggested that these two clinically important aspects of immunological dysregulations are attributable to common molecular mechanisms.…”

Residual serum fibrinogen as a universal biomarker for all serotypes of Myasthenia gravis

“…Potential cross-reactivity of auto-antibodies to fibrinogen may protect fibrinogen from activation, but this seems unlikely as it appears to occur with all serotypes. Interestingly, a previous proteome-wide screening for cross-reactivity of autoantibodies in MG patients failed to report fibrinogen as a potential target 38 . Nonetheless, other factors may bind fibrinogen and preclude its conversion to fibrin.…”