Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations.
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.
Wagenaar-Bos
Ineke G A
IG
Department of Immunopathology, University of Amsterdam, Amsterdam, The Netherlands. i.bos@sanquin.nl
Drouet
Christian
C
Aygören-Pursun
Emel
E
Bork
Konrad
K
Bucher
Christoph
C
Bygum
Anette
A
Farkas
Henriette
H
Fust
George
G
Gregorek
Hanna
H
Hack
C Erik
CE
Hickey
Alaco
A
Joller-Jemelka
Helen I
HI
Kapusta
Maria
M
Kreuz
Wolfhart
W
Longhurst
Hilary
H
Lopez-Trascasa
Margarita
M
Madalinski
Kazimierz
K
Naskalski
Jerzy
J
Nieuwenhuys
Ed
E
Ponard
Denise
D
Truedsson
Lennart
L
Varga
Lilian
L
Nielsen
Erik Waage
EW
Wagner
Eric
E
Zingale
Lorenza
L
Cicardi
Marco
M
van Ham
S Marieke
SM
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
D003174:Complement C1 Inactivator Proteins