| Autor: |
Dechomet M; Service d'Immunologie biologique, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon et Université Claude Bernard-Lyon 1, Lyon, France., Zerimech F; CHU Lille, Service de Biochimie Biologie Moléculaire, Institut Pasteur Lille, Univ. Lille, ULR 4483 - IMPECS - IMPact de l'Environnement Chimique sur la Santé humaine, F-59000 Lille, France., Chapuis-Cellier C; Service d'Immunologie biologique, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon et Université Claude Bernard-Lyon 1, Lyon, France., Lombard C; Service d'Immunologie biologique, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon et Université Claude Bernard-Lyon 1, Lyon, France., Balduyck M; CHU Lille, Service de Biochimie Biologie Moléculaire, Univ. Lille, Laboratoire de Biochimie Biologie moléculaire, ULR 7364 - RADEME - Maladies RAres du DÉveloppement embryonnaire et du Métabolisme, F-59000 Lille, France. |
| Abstrakt: |
The existence of alpha-1 antitrypsin variants with apparently unremarkable phenotypes and serum concentrations, contrasting with a clinical picture suggestive of a severe deficiency, led us to investigate whether in these cases there was a reduction or even suppression of the capacity of alpha-1 antitrypsin to inhibit elastase. To this end, in two different laboratories, we adapted and validated a method for measuring the functional activity of alpha-1 antitrypsin, based on spectrophotometric kinetic analysis of the inhibition by serum alpha-1 antitrypsin of the hydrolytic activity of porcine pancreatic elastase on a chromogenic substrate. This method has proved to be robust, reproducible and transferable and made possible to define, on the basis of an analysis of a hospital population, a functionality index with a confidence interval comprised between 0.87 and 1.2, allowing to identify subjects likely to have a functional deficiency of alpha-1 antitrypsin, whether this deficiency being of a genetic origin without any quantitative or phenotypic translation, or whether being acquired under the effect of external agents (cigarette smoke or viruses). |
