Immune activation in α1-antitrypsin-deficiency emphysema: Beyond the protease-antiprotease paradigm

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

Research output: Contribution to journalArticlepeer-review


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

Original languageEnglish
Pages (from-to)402-409
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number4
Publication statusPublished - Feb 15 2015


  • Autoimmunity
  • Chronic obstructive pulmonary disease
  • Lymphocytes
  • Lymphoid follicles
  • α-antitrypsin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Medicine(all)


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