Myasthenia gravis (MG) is a neuromuscular disease related to the deleterious action of autoantibodies directed against elements of the neuromuscular junction, most often against the acetylcholine receptor (AChR) which is located in the postsynaptic region. The thymus plays a key role in this pathology (AChR-MG) and is characterised by an IFN-β-related type I interferon (IFN) signature.
In this French study, the authors, among whom were researchers from the “Myasthenia Gravis: etiology, pathophysiology & therapeutic approach” team of the Myology Centre for Research of the Institute of Myology, investigated whether AChR-MG is characterised by an IFN-I signature in the blood; they also studied the chronic thymic IFN-I signature.
In particular, the results showed that :
- no IFN-I signature was observed in the periphery, which underlines that the IFN-I signature is limited to the MG thymus;
- a significant decrease in thymic macrophages was demonstrated in the AChR-MG group;
- in mice, a decrease in thymic macrophages led to an increase in necrotic thymocytes associated with IFN-β and α-AChR expression.
These results suggest that the decrease in thymic macrophages in AChR-MG hinders the elimination of apoptotic thymocytes, which promotes the release of endogenous nucleic acids from necrotic thymocytes. In this inflammatory context, thymus epithelial cells can overexpress IFN-β, which specifically induces α-AChR, leading to self-sensitisation and disease-generating thymic changes.
