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Verfasser:Ferré, Elise [VerfasserIn]   i
 Allgäuer, Michael [VerfasserIn]   i
Titel:Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance
Verf.angabe:Elise M. N. Ferré, Timothy J. Break, Peter D. Burbelo, Michael Allgäuer, David E. Kleiner, Dakai Jin, Ziyue Xu, Les R. Folio, Daniel J. Mollura, Muthulekha Swamydas, Wenjuan Gu, Sally Hunsberger, Chyi-Chia R. Lee, Anamaria Bondici, Kevin W. Hoffman, Jean K. Lim, Kerry Dobbs, Julie E. Niemela, Thomas A. Fleisher, Amy P. Hsu, Laquita N. Snow, Dirk N. Darnell, Samar Ojaimi, Megan A. Cooper, Martin Bozzola, Gary I. Kleiner, Juan C. Martinez, Robin R. Deterding, Douglas B. Kuhns, Theo Heller, Karen K. Winer, Arun Rajan, Steven M. Holland, Luigi D. Notarangelo, Kevin P. Fennelly, Kenneth N. Olivier, Michail S. Lionakis
E-Jahr:2019
Jahr:5 June 2019
Umfang:16 S.
Fussnoten:Gesehen am 16.08.2019
Titel Quelle:Enthalten in: Science translational medicine
Ort Quelle:Washington, DC : AAAS, 2009
Jahr Quelle:2019
Band/Heft Quelle:11(2019,495) Artikel-Nummer eaav5597, 16 Seiten
Abstract:<p>Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by <i>AIRE</i> mutations, presents with several autoimmune diseases. Among these, endocrine organ failure is widely recognized, but the prevalence, immunopathogenesis, and treatment of non-endocrine manifestations such as pneumonitis remain poorly characterized. We enrolled 50 patients with APECED in a prospective observational study and comprehensively examined their clinical and radiographic findings, performed pulmonary function tests, and analyzed immunological characteristics in blood, bronchoalveolar lavage fluid, and endobronchial and lung biopsies. Pneumonitis was found in >40% of our patients, presented early in life, was misdiagnosed despite chronic respiratory symptoms and accompanying radiographic and pulmonary function abnormalities, and caused hypoxemic respiratory failure and death. Autoantibodies against BPIFB1 and KCNRG and the homozygous c.967_979del13 <i>AIRE</i> mutation are associated with pneumonitis development. APECED pneumonitis features compartmentalized immunopathology, with accumulation of activated neutrophils in the airways and lymphocytic infiltration in intraepithelial, submucosal, peribronchiolar, and interstitial areas. Beyond APECED, we extend these observations to lung disease seen in other conditions with secondary AIRE deficiency (thymoma and RAG deficiency). Aire-deficient mice had similar compartmentalized cellular immune responses in the airways and lung tissue, which was ameliorated by deficiency of T and B lymphocytes. Accordingly, T and B lymphocyte-directed immunomodulation controlled symptoms and radiographic abnormalities and improved pulmonary function in patients with APECED pneumonitis. Collectively, our findings unveil lung autoimmunity as a common, early, and unrecognized manifestation of APECED and provide insights into the immunopathogenesis and treatment of pulmonary autoimmunity associated with impaired central immune tolerance.</p>
DOI:doi:10.1126/scitranslmed.aav5597
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1126/scitranslmed.aav5597
 Volltext: https://stm.sciencemag.org/content/11/495/eaav5597
 DOI: 10.1126/scitranslmed.aav5597
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1671527356
Verknüpfungen:→ Zeitschrift

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