Alpha-1 Antitrypsin Deficiency Today: New Insights in the Immunological Pathways
2016; Karger Publishers; Volume: 91; Issue: 5 Linguagem: Inglês
10.1159/000445692
ISSN1423-0356
AutoresSimonetta Baraldo, Elisabetta Balestro, Erica Bazzan, Maria Enrica Tiné, Davide Biondini, Graziella Turato, Manuel G. Cosío, Marina Saetta,
Tópico(s)Pulmonary Hypertension Research and Treatments
ResumoMore than 50 years ago, the observation that absence of the α<sub>1</sub> band from protein electrophoresis is associated with severe emphysema established the link between α<sub>1</sub>-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.
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