title: Ectodysplasin A in Biological Fluids and Diagnosis of Ectodermal Dysplasia.
abstract: The tumor necrosis factor (TNF) family ligand ectodysplasin A (EDA) is produced as 2 full-length splice variants, EDA1 and EDA2, that bind to EDA receptor (EDAR) and X-linked EDA receptor (XEDAR/EDA2R), respectively. Inactivating mutations in Eda or Edar cause hypohidrotic ectodermal dysplasia (HED), a condition characterized by malformations of the teeth, hair and glands, with milder deficiencies affecting only the teeth. EDA acts early during the development of ectodermal appendages-as early as the embryonic placode stage-and plays a role in adult appendage function. In this study, the authors measured EDA in serum, saliva and dried blood spots. The authors detected 3- to 4-fold higher levels of circulating EDA in cord blood than in adult sera. A receptor binding-competent form of EDA1 was the main form of EDA but a minor fraction of EDA2 was also found in fetal bovine serum. Sera of EDA-deficient patients contained either background EDA levels or low levels of EDA that could not bind to recombinant EDAR. The serum of a patient with a V262F missense mutation in Eda, which caused a milder form of X-linked HED (XLHED), contained low levels of EDA capable of binding to EDAR. In 2 mildly affected carriers, intermediate levels of EDA were detected, whereas a severely affected carrier had no active EDA in the serum. Small amounts of EDA were also detectable in normal adult saliva. Finally, EDA could be measured in spots of wild-type adult or cord blood dried onto filter paper at levels significantly higher than that measured in EDA-deficient blood. Measurement of EDA levels combined with receptor-binding assays might be of relevance to aid in the diagnosis of total or partial EDA deficiencies.
authors.affiliation: 1 Department of Pediatrics, University Hospital Erlangen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Podzus
authors.affiliation: 2 Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Kowalczyk-Quintas
authors.affiliation: 2 Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Schuepbach-Mallepell
authors.affiliation: 2 Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Willen
authors.affiliation: 2 Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Staehlin
authors.affiliation: 2 Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Vigolo
authors.affiliation: 2 Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Tardivel
authors.affiliation: 3 Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK.
authors.forename: D
authors.initials: D
authors.lastname: Headon
authors.affiliation: 4 Edimer Pharmaceuticals, Cambridge, MA.
authors.forename: N
authors.initials: N
authors.lastname: Kirby
authors.affiliation: 5 Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: M L
authors.initials: ML
authors.lastname: Mikkola
authors.affiliation: 1 Department of Pediatrics, University Hospital Erlangen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Schneider
authors.affiliation: 2 Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D015153:Blotting, Western; D002417:Cattle / Q000097:blood; D059788:Dried Blood Spot Testing; D004476:Ectodermal Dysplasia / Q000175:diagnosis* / Q000235:genetics; D053331:Ectodysplasins / Q000032:analysis* / Q000097:blood; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D012463:Saliva / Q000737:chemistry; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053331:Ectodysplasins
keywords: X-linked; dried blood spot analysis; genetic disease; glycosylation; saliva; serum