Immunoglobulin G Deficiency in United Kingdom Children With Invasive Pneumococcal Disease

Abstract

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. 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. 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. 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.