Laboratory investigation of hybrid igg4 k/λ in musk positive myasthenia gravis

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.