5 Year Expression and Neutrophil Defect Repair after Gene Therapy in Alpha-1 Antitrypsin Deficiency.

Replacement therapy of alpha 1-antitrypsin deficiency. Reversal of protease-antiprotease imbalance within the alveolar structures of PiZ subjects.

The emphysema associated with the inherited serum deficiency of alpha 1-antitrypsin appears to result from an imbalance between neutrophil elastase and its major inhibitor within the alveolar structures. In the present study we assessed the feasibility of reversing this biochemical defect within the lung via parenteral replacement therapy with an alpha 1-antitrypsin concentrate of normal plasma...

Class I-restricted T-cell responses to a polymorphic peptide in a gene therapy clinical trial for alpha-1-antitrypsin deficiency

Dysregulated neutrophil function in individuals with alpha-1 antitrypsin deficiency caused by modified membrane cholesterol content.

Background Individuals with alpha-1 antitrypsin (AAT) deficiency (AATD) are predisposed to early-onset emphysema and neutrophils are the primary effector cells responsible for the pathological manifestations of AATD lung disease. As AAT interacts directly with the circulating neutrophil membrane [1], the question that this project addressed was: are AATD neutrophils structurally and functionall...

Alpha-1 antitrypsin regulates neutrophil reactive oxygen species production via inhibition of key players of the respiratory burst oxidase system

Background Activation of neutrophils sequestered in the alveolar milieu can cause the release of reactive oxygen species (ROS), increasingly regarded as key substances modulating epithelium dysfunction and disruption. These oxidants are generated by the neutrophil respiratory burst oxidase system that reduces molecular oxygen (O2) to superoxide (O2-). Alpha-1 antitrypsin (AAT) deficiency (AATD)...

Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency

INTRODUCTION — Alpha-1 antitrypsin (AAT) deficiency is a clinically underrecognized inherited disorder affecting the lung, liver, and rarely skin. The characteristics of the pulmonary manifestations of this disorder will be reviewed here [1-4]. Extrapulmonary disease and therapy are discussed separately. (See "Extrapulmonary manifestations of alpha-1 antitrypsin deficiency" and "Treatment of al...