title: Properdin deficiency associated with recurrent otitis media and pneumonia, and identification of male carrier with Klinefelter syndrome.
abstract: Properdin is an initiator and stabilizer of the alternative complement activation pathway (AP). Deficiency of properdin is a rare X-linked condition characterized by increased susceptibility to infection with Neisseria meningitidis associated with a high mortality rate. We report properdin deficiency in a large Pakistani family. The index cases were found by screening for immunodeficiency due to a history of recurrent infections. This revealed absent AP activity, but normal classical and lectin pathway activity. Sequencing of the properdin gene (PFC) revealed a novel frameshift mutation. When all available relatives (n=24) were screened for the mutation, four affected males, four female carriers and a male heterozygous carrier were identified. He was subsequently diagnosed with Klinefelter syndrome. A questionnaire revealed a striking association between properdin deficiency and recurrent otitis media (P=0.0012), as well as recurrent pneumonia (P=0.0017). This study is the first to show a significant association between properdin deficiency and recurrent infections.
authors.affiliation: Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Denmark. l.schejbel@gmail.com
authors.forename: Lone
authors.initials: L
authors.lastname: Schejbel
authors.forename: Vibeke
authors.initials: V
authors.lastname: Rosenfeldt
authors.forename: Hanne
authors.initials: H
authors.lastname: Marquart
authors.forename: Niels Henrik
authors.initials: NH
authors.lastname: Valerius
authors.forename: Peter
authors.initials: P
authors.lastname: Garred