%0 Journal Article %T Risk factors associated with myasthenia gravis in thymoma patients: The potential role of thymic germinal centers %+ Centre de recherche en Myologie – U974 SU-INSERM %+ Immunobiologie des Cellules dendritiques %+ Centre Chirurgical Marie Lannelongue (CCML) %+ Université Paris-Sud - Paris 11 (UP11) %+ Hôpital Cochin [AP-HP] %+ Université Paris Descartes - Paris 5 (UPD5) %+ Institut Mutualiste de Montsouris (IMM) %+ Institut de Myologie %A Lefeuvre, Claire Mj %A Payet, Cloé %A Fayet, Odessa-Maud %A Maillard, Solène %A Truffault, Frédérique %A Bondet, Vincent %A Duffy, Darragh %A de Montpreville, Vincent %A Ghigna, Maria-Rosa %A Fadel, Elie %A Mansuet-Lupo, Audrey %A Alifano, Marco %A Validire, Pierre %A Gossot, Dominique %A Behin, Anthony %A Eymard, Bruno %A Berrih-Aknin, Sonia %A Le Panse, Rozen %Z This work was supported by grants from the European Community (FIGHT-MG/HEALTH-2009-242-210), from the “Association Française contre les Myopathies” (AFM), and from the “Agence Nationale de la Recherche” (ANR grant number CE17001002). %< avec comité de lecture %@ 0896-8411 %J Journal of Autoimmunity %I Elsevier %V 106 %P 102337 %8 2020-01 %D 2020 %R 10.1016/j.jaut.2019.102337 %M 31594658 %K Autoimmune diseases %K Cytokines %K Myasthenia gravis %K Paraneoplastic syndromes %K Tertiary lymphoid structures %K Thymus %Z Life Sciences [q-bio]/ImmunologyJournal articles %X Thymomas are associated with a very high risk of developing Myasthenia Gravis (MG). Our objectives were to identify histological and biological parameters to allow early diagnosis of thymoma patients susceptible to developing MG. We 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). We also performed multiplex and single molecule arrays to measure the serum levels of cytokines in these groups of patients and controls (n = 14-22). 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 these parameters, 58.8% of MGT patients displayed GCs with a positive correlation between the number of GCs and anti-AChR titers. By immunohistochemistry, we found thymic GCs in the adjacent tissues of thymomas 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 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. %G English %Z We thank Mathieu Surenaud and Sophie Hüe from the immunomonitoring platform (IMRB, VRI, INSERM U955 - UPEC, France) for Bio-Plex analyses. DD thanks ImmunoQure AG for sharing the antibodies to assess IFN-α protein levels in the Simoa assay. AM-L and VM are expert members of the RYTHMIC network (“Réseau Tumeurs THYmiques et Cancer”). %2 https://pasteur.hal.science/pasteur-02315094/document %2 https://pasteur.hal.science/pasteur-02315094/file/S0896841119305281.pdf %L pasteur-02315094 %U https://pasteur.hal.science/pasteur-02315094 %~ INSERM %~ PASTEUR %~ CEA %~ CNRS %~ UNIV-PSUD %~ APHP %~ U974 %~ DSV %~ UNIV-PARIS-SACLAY %~ UNIV-PSUD-SACLAY %~ CEA-DRF %~ CHU-UNIV-PARIS5 %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ SU-MEDECINE %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ TEST-HALCNRS %~ UNIVERSITE-PARIS-SACLAY %~ SU-TI %~ ELSEVIER %~ ALLIANCE-SU %~ U974-E7