Clinical and Immunologic Characteristics of Healthy Children with Subnormal Serum Concentrations of IgG2

Abstract

ABSTRACT. To understand the relevance of subnormal serum concentrations of IgG2, we measured IgG2 in serum of 575 healthy children and identified 11 with concentrations >2 SD less than the mean for age. The levels of IgG2 present were similar to those found in symptomatic children with IgG2 subclass deficiency associated with antibody deficiency. The 11 children ranged in age from 1 to 14 y (mean = 5.7). Detailed clinical information was available on 10 of the 11 children and each was matched for age with two controls. The median number of visitsly to the doctor for infectious illnesses was identical for the two groups (1.0). Nine of the children with subnormal IgG2 were followed for 1 to 5 y (mean = 2.3). All nine children had normal serum concentrations of IgA, IgG1, IgG3, and IgG4 but seven had persistently subnormal or low-normal serum IgG2 concentrations. One of these seven children also had a subnormal serum concentration of IgG, and one had subnormal IgM. Antibody responses to Haemophilus b polysaccharide vaccine were normal in five of six who were immunized. In vitro secretion of Ig by mitogen-stimulated peripheral blood mononuclear cells was measured in six of seven children with persistently subnormal or lownormal IgG2; five showed decreased secretion of IgG2, and two of the five also had subnormal secretion of IgGl and IgG3. An important implication of this study is that the subnormal concentrations of serum IgG2 found in infectionprone children are not a sufficient explanation for their increased susceptibility to infection. The healthy children with low serum concentrations of IgG2 differ from symptomatic children with subnormal IgG2 in that the former have otherwise normal serum Ig concentrations and have normal antibody responses to Hib P S vaccine.

Antibody response to pneumococcal capsular polysaccharide vaccine in Down syndrome patients

“…Two DS children, aged 8 and 10 years, had serum IgG2 levels below the 3rd percentile but showed an adequate increase of pneumococcal antibodies after immunization. Subnormal serum IgG2 levels do not necessarily reflect a functional immunodeficiency (21,22). An adequate response to pneumococcal antigens depends on an interaction between innate and adaptive immune responses.…”

Pathogenesis, Diagnosis, and Management of Primary Antibody Deficiencies and Infections

“…Since IgG2 is the isotype that is primarily responsible for responses against polysaccharides, it was postulated that a deficiency of this subclass in children would predispose patients to infections with encapsulated bacteria. However, some studies identified children with low IgG2 levels in the healthy population without evidence of increased susceptibility to infections (127). Another study revealed a resolution of IgG2 deficiency in all children observed over a time period of 6 years (6).…”

Are there any clinical indications for measuring IgG subclasses?

“…Failure to produce antibodies in response to vaccination with bacterial proteins and polysaccharides is a better indication of susceptibility to infection. 9 The majority of children who failed to respond to vaccination with the capsular polysaccharide (polyribose phosphate) of HIB (HIB-PRP) had normal IgG 2 subclass concentrations. 21,22 Furthermore, IgG 1 is more e¤cient on a molar basis in activating e¡ector mechanisms like the classical pathway of the complement system and interaction with the relevant Fc receptors on phagocytic cells.…”