title: Immunoglobulin G deficiency in United kingdom children with invasive pneumococcal disease.
abstract: BACKGROUND
  This study aimed to determine whether nonprotective, convalescent pneumococcal serotype-specific immunoglobulin G (IgG) concentrations in children with invasive pneumococcal disease (IPD) might be associated with an underlying IgG deficiency.
  
  
  METHODS
  The first 200 convalescent blood samples from children with IPD that were submitted for pneumococcal antibody testing also had total serum IgG concentrations measured. Pneumococcal IgG testing was performed for 12 serotypes (1, 3, 5, 7, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F); serotype-specific pneumococcal IgG concentrations <0.35 μg/mL were considered nonprotective. IgG deficiency was defined as total serum IgG ≥2 standard deviations below the mean for age.
  
  
  RESULTS
  Nineteen of 172 children (11.0%) with sufficient serum had IgG deficiency although serum IgG concentrations were only marginally below the lower limit for age and all 19 had IgG concentrations >2.0 g/L. IgG deficiency was associated with younger age at disease (median, 5.2 [interquartile range, 2.3-13.5] vs. 12.5 [7.4-17.0] months; P = 0.005) and nonprotective convalescent antibody concentrations against the infecting serotype (10/13 [77%] vs. 51/105 [49%]; P = 0.05). There was a correlation between IgG deficiency and the number of serotypes against which children had nonprotective pneumococcal antibody concentrations, particularly among vaccinated cases (P < 0.05). Vaccine failure was also twice as common among those with IgG deficiency (3/19 [16%] vs. 11/53 [7%], P = 0.20), although this association was not statistically significant. Three children with IgG deficiency who were retested 3 to 5 months later had normal serum IgG concentrations.
  
  
  CONCLUSIONS
  Although 11% of children with IPD had IgG deficiency, total serum IgG concentrations were reassuringly only marginally below the reference range and were within the normal range in those who were retested, suggesting a transient deficiency rather than a serious underlying primary immunodeficiency.
authors.affiliation: Vaccine Evaluation Unit, Health Protection Agency, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Manchester, United Kingdom.
authors.forename: Elaine
authors.initials: E
authors.lastname: Stanford
authors.forename: Shamez
authors.initials: S
authors.lastname: Ladhani
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Pauline
authors.initials: P
authors.lastname: Waight
authors.forename: Mary
authors.initials: M
authors.lastname: Slack
authors.forename: Robert
authors.initials: R
authors.lastname: George
authors.forename: Paul
authors.initials: P
authors.lastname: Balmer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miller
authors.forename: Matthew
authors.initials: M
authors.lastname: Helbert
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D005260:Female; D006801:Humans; D017099:IgG Deficiency / Q000150:complications* / Q000453:epidemiology*; D007074:Immunoglobulin G / Q000097:blood*; D007223:Infant; D008297:Male; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000209:etiology*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G