Immune Activation in α1-Antitrypsin-Deficiency Emphysema. Beyond the Protease–Antiprotease Paradigm

• DOI: 10.1164/rccm.201403-0529oc
• Publication Date: 2014-11-20T22:22:03Z
• Authors: Simonetta Baraldo; Graziella Turato; Francesca Lunardi; Erica Bazzan; Marco Schiavon; Ilaria Ferrarotti; Beatrice Molena; Riccardo Cazzuffi; Marco Damin; Elisabetta Balestro; Maurizio Luisetti; Federico Rea; Fiorella Calabrese; Manuel G. Cosio; Marina Saetta
• Keywords: Alpha 1-antitrypsin deficiency; Neutrophil elastase

α1-Antitrypsin (AAT) is a potent protease inhibitor, deficiency of which associated with the presence emphysema. An imbalance elastase and antielastase, along innate inflammation in lung, believed to cause lung destruction α1-antitrypsin (AATD). It now apparent that AAT has important immune-regulatory roles would be lost AATD, yet adaptive immune responses have not been investigated patients AATD.To assess response severe AATD emphysema compare it present "usual" chronic obstructive pulmonary disease (COPD).The inflammatory explanted lungs from 10 subjects was characterized quantified, results were compared those 26 usual COPD 17 smoking 11 nonsmoking control normal function.Lymphoid follicles (LFs) markedly increased when groups. Molecular analysis B lymphocytes LFs showed predominantly mono/oligoclonality. LF number correlated negatively FEV1/FVC. CD4(+) CD8(+) T significantly IL-32, an cytokine induction autoimmunity, up-regulated COPD.An inflammation, comprising B, CD4(+), lymphocytes, LFs, prominent feature AATD. These change paradigm mechanism AATD-induced pure elastase-antielastase much more complex one involving system, similarly what occurs COPD.