title: Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations.
abstract: Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The most widespread underlying genetic deficiency is a heterozygous deficiency of the serine protease inhibitor C1 esterase inhibitor (C1-Inh). In addition to low C4 levels, the most important laboratory parameter for correct diagnosis of HAE or angioedema due to acquired C1-Inh deficiency is reduced C1-Inh function (fC1-Inh). No direct recommendations about the assays for fC1-Inh or sample handling conditions are available, although this would prove especially useful when a laboratory first starts to offer assays on fC1-Inh for HAE diagnosis. In the present study we evaluated the performance of fC1-Inh assays in the 15 different laboratories that are specialised in HAE diagnostics and assessed inter-laboratory variation with each laboratory using their own assays and standards. A double-blind survey was conducted using plasma/serum samples from healthy donors and HAE patients and the uniformity of HAE diagnosis was evaluated. It can be concluded that the diagnosis of fC1-Inh deficiency was made correctly in most cases in this survey. We can recommend the chromogenic assay for the determination of fC1-Inh, while the complex ELISA needs further investigation.
authors.affiliation: Department of Immunopathology, University of Amsterdam, Amsterdam, The Netherlands. i.bos@sanquin.nl
authors.forename: Ineke G A
authors.initials: IG
authors.lastname: Wagenaar-Bos
authors.forename: Christian
authors.initials: C
authors.lastname: Drouet
authors.forename: Emel
authors.initials: E
authors.lastname: Aygören-Pursun
authors.forename: Konrad
authors.initials: K
authors.lastname: Bork
authors.forename: Christoph
authors.initials: C
authors.lastname: Bucher
authors.forename: Anette
authors.initials: A
authors.lastname: Bygum
authors.forename: Henriette
authors.initials: H
authors.lastname: Farkas
authors.forename: George
authors.initials: G
authors.lastname: Fust
authors.forename: Hanna
authors.initials: H
authors.lastname: Gregorek
authors.forename: C Erik
authors.initials: CE
authors.lastname: Hack
authors.forename: Alaco
authors.initials: A
authors.lastname: Hickey
authors.forename: Helen I
authors.initials: HI
authors.lastname: Joller-Jemelka
authors.forename: Maria
authors.initials: M
authors.lastname: Kapusta
authors.forename: Wolfhart
authors.initials: W
authors.lastname: Kreuz
authors.forename: Hilary
authors.initials: H
authors.lastname: Longhurst
authors.forename: Margarita
authors.initials: M
authors.lastname: Lopez-Trascasa
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Madalinski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Naskalski
authors.forename: Ed
authors.initials: E
authors.lastname: Nieuwenhuys
authors.forename: Denise
authors.initials: D
authors.lastname: Ponard
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Lilian
authors.initials: L
authors.lastname: Varga
authors.forename: Erik Waage
authors.initials: EW
authors.lastname: Nielsen
authors.forename: Eric
authors.initials: E
authors.lastname: Wagner
authors.forename: Lorenza
authors.initials: L
authors.lastname: Zingale
authors.forename: Marco
authors.initials: M
authors.lastname: Cicardi
authors.forename: S Marieke
authors.initials: SM
authors.lastname: van Ham
mesh_terms: D000799:Angioedema / Q000175:diagnosis* / Q000235:genetics; D001800:Blood Specimen Collection; D003174:Complement C1 Inactivator Proteins / Q000032:analysis* / Q000172:deficiency; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D013696:Temperature
chemical_list: D003174:Complement C1 Inactivator Proteins