Risk factors associated with myasthenia gravis in thymoma patients: the potential role of thymic germinal centers

Thymomas are associated with a very high risk of developing Myasthenia Gravis (MG). The objectives of this study were to identify histological and biological parameters to allow early diagnosis of thymoma patients susceptible to developing MG.

A team of French clinicians and researchers, led by Rozen Le Panse and Sonia Berrih-Aknin from the Institute of Myology, conducted a detailed retrospective analysis from a patient database, searching for differences between patients with thymoma-associated MG (MGT, n = 409) and thymoma without MG (TOMA, n = 111) in comparison with nonthymomatous MG patients (MG, n = 1246). They also performed multiplex and single molecule arrays to measure the serum levels of cytokines in these groups of patients and controls (n = 14-22).

The authors identified a set of parameters associated with MG development in thymoma patients:

  • detection of anti-acetylcholine receptor (AChR) antibodies,
  • development of B1 or B2 thymoma subtypes,
  • presence of ectopic thymic germinal centers (GCs),
  • local invasiveness of thymoma,
  • being a woman under 50 years old.

Among these parameters, 58.8% of MGT patients displayed GCs with a positive correlation between the number of GCs and anti-AChR titers. By immunohistochemistry, the researchers found thymic GCs in the adjacent tissues of thymomas encircled by high endothelial venules (HEVs) that could favor peripheral cell recruitment. They also clearly associated MG symptoms with higher IFN-γ, IL-1β and sCD40L serum levels, specifically in MGT patients compared to TOMA patients.

Altogether, these analyses allowed the clear identification of histological, in particular the presence of GCs, and biological parameters that would facilitate the evaluation of the probability of the MG outcome postoperatively in thymoma patients.


Risk factors associated with myasthenia gravis in thymoma patients: The potential role of thymic germinal centers. Lefeuvre CM, Payet CA, Fayet OM, Maillard S, Truffault F, Bondet V, Duffy D, de Montpreville V, Ghigna MR, Fadel E, Mansuet-Lupo A, Alifano M, Validire P, Gossot D, Behin A, Eymard B, Berrih-Aknin S, Le Panse R. J Autoimmun. 2019 Oct 5:102337. doi: 10.1016/j.jaut.2019.102337. [Epub ahead of print]