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Autoimmunity and Immunodeficiency AUTOIMMUNITY AND IMMUNODEFICIENCY Topic Editors Luigi D. Notarangelo and Rosa Bacchetta IMMUNOLOGY FRONTIERS COPYRIGHT STATEMENT ABOUT FRONTIERS © Copyright 2007-2013 Frontiers is more than just an open-access publisher of scholarly articles: it is a pioneering Frontiers Media SA. All rights reserved. approach to the world of academia, radically improving the way scholarly research is managed. All content included on this site, The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share such as text, graphics, logos, button and generate knowledge. Frontiers provides immediate and permanent online open access to all icons, images, video/audio clips, downloads, data compilations and its publications, but this alone is not enough to realize our grand goals. software, is the property of or is licensed to Frontiers Media SA (“Frontiers”) or its licensees and/or subcontractors. 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For the full conditions see the WHAT ARE FRONTIERS RESEARCH TOPICS? Conditions for Authors and the Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are Conditions for Website Use. collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot ISSN 1664-8714 research area! ISBN 978-2-88919-164-2 Find out more on how to host your own Frontiers Research Topic or contribute to one as an DOI 10.3389/978-2-88919-164-2 author by contacting the Frontiers Editorial Office: [email protected] Frontiers in Immunology August 2013 | Autoimmunity and Immunodeficiency | 1 AUTOIMMUNITY AND IMMUNODEFICIENCY Topic Editors: Luigi D. Notarangelo, Harvard Medical School, USA Rosa Bacchetta, Fondazione Centro San Raffaele Del Monte Tabor, Italy Immune regulation results from a finely tuned network of distinct mechanisms operating throughout life and balancing the need to clear infections and prevent self-aggression. Primary Immunodeficiencies (PIDs) are “experiments of nature” where the ability to fight against pathogens is deeply impaired. The study of patients with PIDs has been instrumental to identify and characterize key components and mechanisms Image created by Aisha Sauer and Luigi D. Notarangelo using that govern development Servier Medical Art. and function of the human immune system. Recently, it has become clear that in congenital monogenic diseases the ability of the immune system to build and maintain active tolerance to self can be specifically altered, so that autoimmune symptoms may easily prevail over infections in these pathologies. In addition, increasing observations have brought the attention to the fact that hypomorphic mutations in genes that control T and/or B cell development are often associated with clinical and laboratory features of immune dysregulation, thus expanding the spectrum of PID phenotypes. For example, mutations in genes driving T cell development can lead to defective lymphostromal cross-talk in the thymus and impinge of negative selection of self-reactive T cells and/or Treg function. Similarly, disorders of B cell development may associate with defects of receptor editing and/ or with abnormalities of peripheral B cell homeostasis. On the other hand, autoantibodies can provoke defective immune responses by targeting cytokines and/or immune cells. Frontiers in Immunology August 2013 | Autoimmunity and Immunodeficiency | 2 This Research Topic will focus on i) summarizing updated clinical and immunological features of diseases characterized by immune dysregulation of known and still undefined origin and ii) gathering new insights into the mechanisms of T and B cell development, function and interaction, in order to broader the comprehension of the pathogenesis of autoimmunity and to ultimately advance the definition of novel therapeutic strategies. Frontiers in Immunology August 2013 | Autoimmunity and Immunodeficiency | 3 Table of Contents 05 Immunodeficiency with Autoimmunity: Beyond the Paradox R. Bacchetta and L. D. Notarangelo 06 Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome: A Paradigm of Immunodeficiency with Autoimmunity Federica Barzaghi, Laura Passerini and Rosa Bacchetta 31 Autoimmunity in Wiskott–Aldrich Syndrome: An Unsolved Enigma Marco Catucci, Maria Carmina Castiello, Francesca Pala, Marita Bosticardo and Anna Villa 45 Autoimmune Dysregulation and Purine Metabolism in Adenosine Deaminase Deficiency Aisha Vanessa Sauer, Immacolata Brigida, Nicola Carriglio and Alessandro Aiuti 64 The STAT5b Pathway Defect and Autoimmunity Takahiro Kanai, Jennifer Jenks and Kari Christine Nadeau 72 APECED: Is This a Model for Failure of T Cell and B Cell Tolerance? Nicolas Kluger, Annamari Ranki and Kai Krohn 84 Pathogenesis of Autoimmunity in Common Variable Immunodeficiency Klaus Warnatz and Reinhard E. Voll 90 Autoimmune Cytopenias In Common Variable Immunodeficiency Jenna C. Podjasek and Roshini S. Abraham 97 TH17 Cells in Autoimmunity and Immunodeficiency: Protective or Pathogenic? Ashish K. Marwaha, Nicole J. Leung, Alicia N. McMurchy and Megan K. Levings 105 Dendritic Cells a Double-Edge Sword in Autoimmune Responses Giada Amodio and Silvia Gregori Frontiers in Immunology August 2013 | Autoimmunity and Immunodeficiency | 4 EDITORIAL published: 12 April 2013 doi: 10.3389/fimmu.2013.00077 Immunodeficiency with autoimmunity: beyond the paradox R. Bacchetta 1* and L. D. Notarangelo 2* 1 San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy 2 Division of Immunology and the Manton Center for Orphan Disease Research, Children’s Hospital Boston, Harvard Medical School, Boston, MA, USA *Correspondence: [email protected]; [email protected] Edited by: Eric Meffre, Yale University School of Medicine, USA Reviewed by: Eric Meffre, Yale University School of Medicine, USA The association of immunodeficiency and autoimmunity may Autoimmune polyendocrinopathy-candidiasis-ectodermal dystro- represent a paradox, yet it has been described in an increasing num- phy (APECED) is an autosomal recessive condition due to mutation ber of conditions. Use of unbiased genomic approach to identify of the Autoimmune regulator (AIRE) gene. Patients with APECED novel forms of primary immunodeficiencies (PIDs), along with in- present with predominant organ specificaut oimmunity and autoanti- depth functional studies in biological samples from affected indi- bodies with multiple specificities. AIRE has been shown to play a criti- viduals continue to unravel novel mechanisms underlying immune cal role in allowing expression of self-antigens in the thymus, thereby dysregulation in patients with altered ability of fighting pathogens. permitting deletion of self-reactive T lymphocytes or their diversion In particular, it has been clearly established that genetic defects that to Treg
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