title: Alpha-1 Antitrypsin Deficiency Today: New Insights in the Immunological Pathways.
abstract: More than 50 years ago, the observation that absence of the α1 band from protein electrophoresis is associated with severe emphysema established the link between α1-antitrypsin deficiency (AATD) and lung damage. From this discovery, the classic paradigm of protease/antiprotease imbalance was derived, linking lung destruction in patients with AATD to the unopposed effect of proteases. By extension, this paradigm was also applied to patients with 'common' chronic obstructive pulmonary disease, in whom large increases in smoke-induced proteases could overwhelm the antiprotease capability of AAT. However, it has become increasingly evident that AAT has important anti-inflammatory and immunoregulatory activities which, beside its antiprotease function, may be critically involved in lung destruction. From this perspective, we will consider recent evidence, based on epidemiological, clinical and immunopathological studies, suggesting that it is time to move on from the original protease/antiprotease paradigm toward a more complex view of the condition, which embraces its immunomodulating functions. Of importance, the potent immunoregulatory, tolerogenic role of AAT may support its therapeutic use in a number of diseases other than AATD, particularly in immune-related disorders.
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova and Padova City Hospital, Padova, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Baraldo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Balestro
authors.forename: Erica
authors.initials: E
authors.lastname: Bazzan
authors.forename: Maria Enrica
authors.initials: ME
authors.lastname: Tiné
authors.forename: Davide
authors.initials: D
authors.lastname: Biondini
authors.forename: Graziella
authors.initials: G
authors.lastname: Turato
authors.forename: Manuel G
authors.initials: MG
authors.lastname: Cosio
authors.forename: Marina
authors.initials: M
authors.lastname: Saetta
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008168:Lung / Q000201:enzymology / Q000276:immunology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000276:immunology; D011656:Pulmonary Emphysema / Q000201:enzymology / Q000276:immunology*; D012907:Smoking / Q000276:immunology*; D000515:alpha 1-Antitrypsin / Q000276:immunology*; D019896:alpha 1-Antitrypsin Deficiency / Q000201:enzymology / Q000276:immunology*
chemical_list: D000515:alpha 1-Antitrypsin