title: Immunodeficiency among children with recurrent invasive pneumococcal disease.
abstract: BACKGROUND
  Recurrent invasive pneumococcal disease (rIPD) occurs mostly in children with an underlying disease, but some cases remain unexplained. Immunodeficiency has been described in children with rIPD, but the prevalence is unknown. We used a nationwide registry of all laboratory-confirmed cases of rIPD to identify cases of unexplained rIPD and examine them for immunodeficiency.
  
  
  METHODS
  Cases of rIPD in children 0-15 years of age from 1980 to 2008 were identified. Children without an obvious underlying disease were screened for complement function, T-cell, B-cell, natural killer--cell counts and concentration of immunoglobulins. B-cell function was evaluated by measuring antibody response to polysaccharide-based pneumococcal vaccination and the extent of fraction of somatic hypermutation. Toll-Like receptor (TLR) signaling function and mutations in key TLR-signaling molecules were examined.
  
  
  RESULTS
  In total, rIPD were observed in 54 children (68 cases of rIPD of 2192 IPD cases). Children with classical risk factors for IPD were excluded, and among the remaining 22 children, 15 were eligible for analysis. Of these 6 (40%) were complement C2-deficient. Impaired vaccination response was found in 6 children of whom 3 were C2 deficient. One patient had a severe TLR signaling dysfunction. No mutations in IRAK4, IKBKG or MYD88 were found.
  
  
  CONCLUSIONS
  Of an unselected cohort of children with rIPD at least 11% were C2 deficient. Data suggest that screening for complement deficiencies and deficient antibody response to pneumococcal vaccines in patients with more than 1 episode of IPD is warranted.
authors.affiliation: From the *Department of Microbiological Surveillance and Research, National Neisseria and Streptococcus Reference Center, Statens Serum Institut, Copenhagen, Denmark; †Department of Paediatrics and Adolescent Medicine, ‡Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Denmark; §Department Clinical Biochemistry, Immunology, and Genetics, Statens Serum Institut, Copenhagen, Denmark; and ¶Department of Clinical Microbiology, Slagelse Hospital, Slagelse, Denmark.
authors.forename: Helene
authors.initials: H
authors.lastname: Ingels
authors.forename: Lone
authors.initials: L
authors.lastname: Schejbel
authors.forename: A C
authors.initials: AC
authors.lastname: Lundstedt
authors.forename: Lise
authors.initials: L
authors.lastname: Jensen
authors.forename: Inga A
authors.initials: IA
authors.lastname: Laursen
authors.forename: Lars P
authors.initials: LP
authors.lastname: Ryder
authors.forename: Niels H H
authors.initials: NH
authors.lastname: Heegaard
authors.forename: Helle
authors.initials: H
authors.lastname: Konradsen
authors.forename: Jens Jørgen
authors.initials: JJ
authors.lastname: Christensen
authors.forename: Carsten
authors.initials: C
authors.lastname: Heilmann
authors.forename: Hanne V
authors.initials: HV
authors.lastname: Marquart
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007153:Immunologic Deficiency Syndromes / Q000150:complications*; D007223:Infant; D008297:Male; D009894:Opportunistic Infections / Q000453:epidemiology* / Q000276:immunology*; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000276:immunology*; D012008:Recurrence; D012189:Retrospective Studies; D055815:Young Adult
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