The Autoimmune Regulator AIRE in Thymoma Biology: Autoimmunity and Beyond Alexander Marx, MD, Peter Hohenberger, MD, Hans Hoffmann, MD, Joachim Pfannschmidt,

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Presentation transcript:

The Autoimmune Regulator AIRE in Thymoma Biology: Autoimmunity and Beyond Alexander Marx, MD, Peter Hohenberger, MD, Hans Hoffmann, MD, Joachim Pfannschmidt, MD, Philipp Schnabel, MD, Hans-Stefan Hofmann, MD, Karsten Wiebe, MD, Berthold Schalke, MD, Wilfred Nix, MD, Ralf Gold, MD, Nick Willcox, MD, Pärt Peterson, PhD, Philipp Ströbel, MD Journal of Thoracic Oncology Volume 5, Issue 10, Pages S266-S272 (October 2010) DOI: 10.1097/JTO.0b013e3181f1f63f Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Characteristic histology of the main WHO-defined thymomas that are commonly associated with myasthenia gravis (MG) and/or other autoimmune diseases. a,Type A thymoma; b, type AB thymoma; c-e, type B1 thymoma, H&E: lighter medullary area (med) with a single Hassall's corpuscle (HC) sharply separated from darker cortical (cort) area (c); AIRE+ medullary thymic epithelial cells (brown nuclei) adjacent to HC (d); desmin-positive myoid cells (brown) in the medullary area of a type B1 thymoma (e). f, Type B2 thymoma; g, Type B3 thymoma. H&E (a-c,f,g); immunoperoxidase (d,e). Reprinted with permission from Autoimmunity.12 Journal of Thoracic Oncology 2010 5, S266-S272DOI: (10.1097/JTO.0b013e3181f1f63f) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Correlation of myasthenia gravis (MG) subtypes with thymus/thymoma histology, frequency of AIRE+ medullary thymic epithelial cells (mTECs), and characteristic autoantibodies to acetylcholine receptor (AChR); the striational muscle antigen titin; the sarcoplasmic reticulum calcium channel ryanodine receptor, RyR; and various cytokines (different interferon-alpha subtypes; IFNαs; interleukin 12, IL-12). EOMG, early-onset MG (< disease onset <45 years of age); LOMG, late-onset MG (MG without thymoma and onset at 45 years or later); TAMG, thymoma-associated MG. H&E-stained sections: EOMG and LOMG (×100); thymoma (×400). The thymoma represents a characteristic WHO type B2 thymoma (B2). Journal of Thoracic Oncology 2010 5, S266-S272DOI: (10.1097/JTO.0b013e3181f1f63f) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 AIRE expression in the normal thymus. a, Expression of AIRE (blue) in the nucleus of one of the pancytokeratin-expressing (green; antibodiy AE1/AE3) medullary thymic epithelial cells (mTECs). b, “Promiscuous” expression of thyroglobulin (green) in one of the AIRE-expressing mTECs (blue nuclei). Immunofluorescence (×400). Journal of Thoracic Oncology 2010 5, S266-S272DOI: (10.1097/JTO.0b013e3181f1f63f) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 4 a, Normal expression of AIRE and lymphotoxin-β (LT-β) in the normal thymic medulla. b, Apparently normal expression (mRNA and/or protein) of TRAF6, RANK, RANKL, LT-β, and LT-β-receptor in various thymomas compared with normal thymus. Beta-actin and GAPDH served as loading controls. The indicated factors are known to be required for AIRE expression in the thymus.56–57 Journal of Thoracic Oncology 2010 5, S266-S272DOI: (10.1097/JTO.0b013e3181f1f63f) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions