Chest
Selected ReportsZ α1-Antitrypsin Polymerizes in the Lung and Acts as a Neutrophil Chemoattractant
Section snippets
Study Population
Five patients with A1AT deficiency (PiZZ phenotype), five PiMM control subjects, and one patient with the PiZZ phenotype who had received a liver transplant were evaluated as part of this study. All patients were clinically stable at the time of the study and had been free of infection for the previous 6 weeks. All patients in the study had been phenotyped previously by standard isoelectric focusing techniques. The patient with the liver transplant had undergone transplantation 10 years
Patient Demographics
The study population included five PiZZ patients, whose conditions were confirmed by A1AT levels and isoelectric focusing. Four of the patients were ex-smokers with established lung disease (ie, FEV1, 43 ± 14% predicted; FEV1/FVC ratio, 38 ± 2% predicted; diffusing capacity of the lung for carbon monoxide [Dlco], 34± 12% predicted). One patient was a newly diagnosed nonsmoker (ie, FEV1, 99% predicted; FEV1/FVC ratio, 72% predicted; Dlco, 96% predicted). All patients were men, with an age range
Discussion
This study shows for the first time that A1AT is locally produced on the epithelial surface of the lung. The source of this A1AT could be respiratory epithelial cells, macrophages, or, less likely, neutrophils.910 In addition, unlike MA1AT protein, this ZA1AT protein polymerizes at body temperature, and, in addition to being an ineffective antiprotease inhibitor, may become a strong neutrophil chemoattractant, thus representing an ongoing source of inflammation in the lungs of individuals with
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Alpha-1 antitrypsin deficiency–associated panniculitis
2021, Journal of the American Academy of DermatologyCitation Excerpt :Moreover, Z-AAT polymers are neutrophil chemoattractant30-32 and have been shown at skin biopsy alongside immunoglobulin M and complement C3.33 Studies have shown AAT polymers in the lungs of ZZ individuals34 and that AATD results in an increased influx of neutrophils into the lungs.30,35 These mechanisms may mirror the pathophysiology of AATD-associated panniculitis.
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This research was funded by the American Alpha One Foundation and the Charitable Infirmary Charitable Trust, Health Research Board.