Impaired Antigen-Specific Immune Response to Vaccines in Children with Antibody Production Defects

Abstract

The impaired synthesis of antigen-specific antibodies, which is indispensable for an adaptive immune response to infections, is a fundamental pathomechanism that leads to clinical manifestations in children with antibody production defects. The aim of this study was to evaluate the synthesis of antigen-specific antibodies following immunization in relation to peripheral blood B cell subsets in young children with hypogammaglobulinemia. Twenty-two children, aged from 8 to 61 months, with a deficiency in one or more major immunoglobulin classes participated in the study. Postvaccination antibodies against tetanus and diphtheria toxoids, the surface antigen of the hepatitis B virus, and the capsular Haemophilus influenzae type b polysaccharide antigen were assessed along with an immunophenotypic evaluation of peripheral blood B lymph cell maturation. A deficiency of antibodies against the tetanus toxoid was assessed in 73% of cases and that against the diphtheria toxoid was assessed in 68% of cases, whereas a deficiency of antibodies against the surface antigen of the hepatitis B virus was revealed in 59% of the children included in the study. A defective response to immunization with a conjugate vaccine with the Haemophilus influenzae type b polysaccharide antigen was demonstrated in 55% of hypogammaglobulinemic patients. Increased proportions of transitional B lymph cells and an accumulation of plasmablasts accompanied antibody deficiencies. The defective response to vaccine protein and polysaccharide antigens is a predominating disorder of humoral immunity in children with hypogammaglobulinemia and may result from a dysfunctional state of the cellular elements of the immune system.

FIG 1

Subgroups of patients studied regarding the deficiency of major classes of immunoglobulins.

FIG 2

Individual serum immunoglobulin G (a), A (b), and M (c) levels in children studied. Min, minimum; max, maximum.

FIG 3

Levels of antigen-specific postvaccination antibodies: anti-HBs (a), anti-tetanus toxoid (b), anti-diphtheria toxoid (c), and anti-PRP Hib (d).

FIG 4

Relative values (a) and absolute counts (b) of transitional B lymphocytes in children with hypogammaglobulinemia.

FIG 5

Relative values (a) and absolute counts (b) of plasmablasts in children with hypogammaglobulinemia.