title: [Development of a laboratory test on dried blood spots for facilitating early diagnosis of alpha-1-antitrypsin deficiency].
abstract: Alpha- 1-antitrypsin (A1AT) deficiency is a hereditary autosomal codominant genetic disorder resulting in low circulating levels of A1AT and leading to lung and/or liver disease. It remains underdiagnosed and only 5 to 10% of PIZZ patients, the most common form of severe A1AT deficiency, would be actually identified in France. Facilitating early diagnosis of A1AT deficiency would allow a better management of this disease; therefore we have developed and standardized in three laboratories involved in this study, a diagnostic test on dried blood spots (DBS) including quantitative A1AT measurement, phenotyping by IEF electrophoresis and, if necessary, genotyping by SERPINA1 gene sequencing. We performed a quantitative assay on 90 DBS samples by immunoturbidimetric or immunonephelometric methods. We demonstrated that both methods were suitable for this type of sampling and the results obtained were highly correlated (R(2)>0.9) between the three laboratories: for a target value of 1.00 g/L, the results obtained from the three laboratories were between 1.00 and 1.02 g/L. Phenotyping and genotyping were performed under redefined operating conditions and adapted to the analysis of DBS samples. The results were comparable with those obtained for venous blood samples. Following this work, it becomes possible to provide pulmonologists with a reliable kit to perform a capillary blood sampling on filter paper which would allow a large-scale screening of A1AT deficiency in the population particularly affected by this genetic condition.
authors.affiliation: Laboratoire de biochimie et biologie moléculaire (HMNO), Centre de biologie pathologie, CHRU de Lille, Lille, France, Laboratoire de biochimie et biologie moléculaire, Faculté de pharmacie, Université de Lille 2, Lille, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Balduyck
authors.affiliation: Centre de biologie Sud, Laboratoire d'immunologie, centre hospitalier Lyon Sud, Hospices civils de Lyon & Université Claude Bernard-Lyon 1, Lyon, France.
authors.forename: Colette
authors.initials: C
authors.lastname: Chapuis Cellier
authors.affiliation: Laboratoire de biochimie, Assistance Publique-Hôpitaux de Paris, Hôpital européen Georges Pompidou, Paris, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Roche
authors.affiliation: Laboratoire de biochimie et biologie moléculaire (HMNO), Centre de biologie pathologie, CHRU de Lille, Lille, France, Laboratoire de bactériologie virologie, Faculté de pharmacie, Université de Lille 2, Lille, France.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Odou
authors.affiliation: Laboratoire de biochimie et biologie moléculaire, Unité de pathologie moléculaire du Globule rouge, Hôpital Édouard Herriot, Hospices civils de Lyon & Université Claude Bernard-Lyon 1, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Joly
authors.affiliation: Laboratoire de biochimie, Assistance Publique-Hôpitaux de Paris, Hôpital européen Georges Pompidou, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Madelain
authors.affiliation: Sebia - Diagnostic Department, Evry, France.
authors.forename: Anita
authors.initials: A
authors.lastname: Vergne
authors.affiliation: Sebia - Diagnostic Department, Evry, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Nouadje
authors.affiliation: Service de pneumologie et oncologie thoracique, Hôpital A. Calmette, CHRU de Lille, Lille, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lafitte
authors.affiliation: Laboratoire de biochimie et biologie moléculaire (HMNO), Centre de biologie pathologie, CHRU de Lille, Lille, France, Inserm, U837, Centre de recherche Jean-Pierre Aubert, Lille, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Porchet
authors.affiliation: Laboratoire de biochimie, Assistance Publique-Hôpitaux de Paris, Hôpital européen Georges Pompidou, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Beaune
authors.affiliation: Laboratoire de biochimie et biologie moléculaire (HMNO), Centre de biologie pathologie, CHRU de Lille, Lille, France.
authors.forename: Farid
authors.initials: F
authors.lastname: Zerimech
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D059788:Dried Blood Spot Testing / Q000379:methods*; D042241:Early Diagnosis; D005838:Genotype; D006801:Humans; D007118:Immunoassay; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry; D010641:Phenotype; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000097:blood / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood / Q000175:diagnosis*
chemical_list: D000515:alpha 1-Antitrypsin
keywords: SERPINA1; alpha-1-antitrypsin; deficiency; dried blood spot; screening