Background and Aims

Thymomas are associated with a very high risk to develop Myasthenia Gravis (MG). Our objectives were to identify histological and biological parameters allowing an early diagnostic of thymoma patients susceptible to develop MG.

Methods

We conducted a detailed retrospective analysis from our MG patient database (n=1766) searching for differences between patients with thymoma-associated MG (MGT) and thymoma without MG (TOMA), in comparison with MG patients without thymoma (MG). We also performed multiplex and Simoa analyses to measure serum levels for 16 cytokines in these groups of patients and controls (n=14-22).

Results

We identified a set of parameters associated with MG development in thymoma patients: 1) detection of anti-acetylcholine receptor (AChR) antibodies, 2) development of B1 or B2 thymoma subtypes, 3) presence of ectopic thymic germinal centers (GCs), 4) local invasiveness of thymoma, and 5) being a woman under 50 years old. Among all these parameters, 58.8% of MGT patients displayed GCs with a positive correlation between the number of GCs and the anti-AChR titers. By immunohistochemistry, we found thymic GCs in the adjacent tissue of thymoma encircled by high endothelial venules (HEVs) that could favor peripheral cell recruitment. We also clearly associated MG symptoms with higher IFN-γ, IL-1β and sCD40L serum levels specifically in MGT compared to TOMA patients.

Conclusions

Altogether, these analyses had allowed the clear identification of histological, in particular the presence of GCs, and biological parameters that would help to evaluate the probability of the outcome of MG post-operatively in thymoma patients.

Background and Aims

Myasthenia gravis (MG) is a rare neuromuscular disease due to autoantibodies against the acetylcholine receptor (AChR). Thymic abnormalities are associated with MG such as ectopic germinal center development with B cells producing anti-AChR antibodies. The MG thymus is characterized by the overexpression of interferon (IFN)-β and IFN-I induced genes (ISGs). IFN-β orchestrates thymic changes associated with MG and favors the autoimmune reaction against α-AChR. An IFN-I signature is observed in periphery in other autoimmune diseases such as SLE or dermatomyositis. Our objective was to search for an IFN-I signature in periphery in MG patients.

Methods

Serum and PBMCs were collected from early-onset MG (EOMG) patients and age-matched healthy donors. The expression of IFN-α, IFN-β and six ISGs have been measured by RT-qPCR in PBMCs. The serum levels of IFN-α and IFN-β have been measured by Simoa and ELISA.

Results

In PBMCs, no increased expression of IFN-α, IFN-β or of ISGs, except RASD2, were observed in MG either in patients treated or not with corticosteroids or in patients thymectomized or not.

In the serum, no increased expression of IFN-α and IFN-I were observed in MG patients even when patients were stratified according to the severity of the disease or to their treatments (corticosteroids, thymectomy).

Conclusions

Altogether, these results showed that there is no IFN-I signature in PBMCs or in the serum of EOMG patients. The IFN-I signature is confined to the thymus with no apparent release in the periphery.