0000000000671610
AUTHOR
Viola Hoffacker
Expression of the Acetylcholine Receptor α-Subunit Gene is Associated with Paraneoplastic Myasthenia Gravis in Mixed Thymoma
Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction [1]. The muscular AChR has been extensively characterized [2], but the etiology of MG is still obscure. Whether the muscular AChR or another (auto)antigen plays a role during the initiation of MG is unknown [3]. The muscular AChR is a pentameric ion channel composed of four different subunits. The α-subunit contains the acetylcholine binding site and the main epitopes recognized by MG autoantibodies [2]. The human muscle AChR α-subunit exists as two isoforms, P3A- and P3A+ [4]. This is a result of alternative splicing of the P3A exon located betwee…
Neurofilament is an autoantigenic determinant in myasthenia gravis
Intratumorous expression of a 153-kd protein (p153), which contains an acetylcholine receptor-like epitope, is the only tumor marker described to date that significantly associates with thymoma in paraneoplastic myasthenia gravis (MG). Here, we report that p153 is identical to the midsize neurofilament, as verified by immunohistochemistry, immunofluorescence, and western blot analysis. Furthermore, the acetylcholine receptor-like epitope of the midsize neurofilament (NF-M) was identified by peptide epitope mapping. We also show, using T-cell proliferation assays, a significantly increased response of intratumorous T cells to a recombinant midsize neurofilament fragment in thymoma patients w…
Low Levels of Acetylcholine Receptor Delta-Subunit Message and Protein in Human Thymus Suggests the Occurrence of ‘Triplet Receptors’ in Thymic Myoid Cells
Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction [1]. The muscular AChR has been extensively characterized [2], but whether the muscular AChR plays a role during the initiation of MG is unknown [3]. The muscular AChR is a pentameric ion channel composed of 4 different subunits [2, 4]. The fetal AChR expressed during intrauterine life and after denervation of adult muscle exhibits an α2βδγ composition, while the adult AChR expressed after birth in innervated muscle exhibits an α2βδγ composition [4]. The α-subunit contains the main epitopes recognized by MG autoantibodies [2]. The human muscle AChR…