Abstract
Myasthenia gravis with antibodies (Abs) against the muscle-specific tyrosine kinase (MuSK) is a rare autoimmune disorder (AD) of the neuromuscular junction (NMJ) and represents a prototype of AD with proven IgG4-mediated pathogenicity. Thanks to the mechanism of Fab-arm exchange (FAE) occurring in vivo, resulting MuSK IgG4 k/λ Abs increase their interference on NMJ and pathogenicity. The characterization of hybrid MuSK IgG4 as a biomarker for MG management is poorly investigated. Here, we evaluated total IgG4, hybrid IgG4 k/λ, and the hybrid/total ratio in 14 MuSK-MG sera in comparison with 24 from MG with Abs against acetylcholine receptor (AChR) that represents the not IgG4-mediated MG form. In both subtypes of MG, we found that the hybrid/total ratio reflects distribution reported in normal individuals; instead, when we correlated the hybrid/total ratio with specific immune-reactivity we found a positive correlation only with anti-MuSK titer, with a progressive increase of hybrid/total mean values with increasing disease severity, indirectly confirming that most part of hybrid IgG4 molecules are engaged in the anti-MuSK pathogenetic immune-reactivity. Further analysis is necessary to strengthen the significance of this less unknown biomarker, but we retain it is full of a diagnostic-prognostic powerful potential for the management of MuSK-MG.
Highlights
A different profile of serological IgG subclasses has been widely described in patients with autoimmune disorders (AD), increasing the interest to properly understand their contribution in pathogenesis and clinical significance for a different personalized management of disease [1]
We reported our results of a pilot serological analysis aimed to explore the levels of hybrid IgG4 molecules in muscle-specific tyrosine kinase (MuSK)-Myasthenia gravis (MG), in comparison with acetylcholine receptor (AChR)-MG used as a not IgG4-mediated MG control
Despite the very limited number of samples prevents us from any statistical con- 4, we visualized the distribution of Hybrid/Total IgG4 ratios at different MG Foundation of America (MGFA) scores for sideration, we noticed a progressive increase of the titer with the increasing of MGFA
Summary
A different profile of serological IgG subclasses has been widely described in patients (pts) with autoimmune disorders (AD), increasing the interest to properly understand their contribution in pathogenesis and clinical significance for a different personalized management of disease [1]. We reported our results of a pilot serological analysis aimed to explore the levels of hybrid IgG4 molecules in MuSK-MG, in comparison with AChR-MG used as a not IgG4-mediated MG control. For this evaluation, we analyzed serum samples from 14 MuSK-MG and 24 AChR-MG pts. We evaluated the relationship between hybrid/total IgG4 ratio with the specific Abs titer in MuSKand AChR-MG, visualized in Figure 3A,B respectively. For this purpose, a linear model was fitted to data and the corresponding regression line is shown together with confidence and prediction bands.
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