Duraiswamy Navaneetham

Human thymuses express incomplete sets of muscle acetylcholine receptor subunit transcripts that seldom include the δ subunit

In myasthenia gravis (MG) the muscle acetylcholine receptor (AChR) is the target of an immune response that might begin in the thymus. The thymus expresses binding sites for specific ligands of muscle AChR, a complex protein composed of α, β, γ (or ϵ) and δ subunits. The thymus expresses the AChR α subunit, but there is controversy regarding the expression in the thymus of the γ, ϵ and δ subunits. We investigated the presence of messenger RNA (mRNA) for the different muscle AChR subunits in thymus tissue from 20 healthy subjects and 13 myasthenic patients. We detected mRNA for the α and ϵ subunits in all samples, for the β subunit in all but one sample and for the γ subunit in most samples although at lower levels than the ϵ subunit. Myasthenic thymuses expressed levels of γ subunit mRNA similar to control thymuses but more abundant ϵ subunit mRNA. None of the myasthenic thymuses and only two control thymuses expressed detectable δ subunit mRNA. This supports the hypothesis that human thymus may express AChR proteins that do not include the δ subunit. Such receptors, which would have different antigenic structure than the muscle AChRs, might have a role in triggering the autoimmune response that causes MG.

Anti-Acetylcholine Receptor CD4+ T Cells in Myasthenia Gravis: Epitope repertoire and T cell receptor gene usage

Although the symptoms of myasthenia gravis (MG) are due to the binding of auto-antibodies to the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction (reviewed in [1]), the anti-AChR CD4+T cells have been intensely investigated, because they may be the prime movers in the pathogenesis of MG. Furthermore, specific immunosuppressive treatments targeted on the autoimmune CD4+ cells have proven successful in experimental autoimmune diseases, including the experimental model of MG, mouse experimental autoimmune MG (EAMG) ([2–4] and references therein).