RISK FACTORS ASSOCIATED WITH MYASTHENIA GRAVIS IN THYMOMA PATIENTS: A LINK WITH ECTOPIC GERMINAL CENTERS
- Cloé Payet, France
Abstract
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.