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. A ntibody production defects are the most common category of pediatric primary immunodeficiencies (PIDs) (1, 2). The hallmark of these immunodeficiency conditions is the defective production of antigen-specific antibodies that are an indispensable element of the adaptive immune response to pathogens (3, 4). While the poor response to vaccines is another feature of humoral PIDs, the ability to synthesize postvaccination antibodies against toxoids and polysaccharides is the most specific expression of the immune response to antigens. In the evaluation of the immune response associated with antibody production, the response to vaccination against hepatitis B is not routinely recommended because of the large proportion of adults, up to between 1% and 3% of vaccinated individuals, who do not effectively synthesize antibodies against hepatitis B virus surface antigen (HBs). In infants and children, the efficiency of recombinant vaccines against hepatitis B, assessed on the basis of postvaccination anti-HBs antibody concentration over 10 mIU/ml, is estimated at 85% to 100% (5, 6). The minimal protective level of neutralizing antibodies against diphtheria and tetanus toxoids has been estimated at 0.01 to 0.1 IU/ml, whereas to achieve long-term immunity, a concentration of specific antibodies, up to 1.0 IU/ml, may be required. The synthesis of...

Measurement of Typhi Vi antibodies can be used to assess adaptive immunity in patients with immunodeficiency

“…50-fold increase in Typhi Vi IgG and 13-fold increase in pneumococcal IgG) was diagnosed with hypogammaglobinaemia and the other patient (with a greater than or equal to fivefold increase in Typhi Vi IgG and a sevenfold increase in pneumococcal IgG) was diagnosed with IgG subclass deficiency. Residual responses to vaccines, sometimes near to those observed in a normal population, have been shown previously in patients with hypogammaglobinaemia [16][17][18]. Total serum immunoglobulin levels alongside the functional information offered by vaccination responses and clinical assessment of infection burden are required to evaluate humoral immune function [19].…”

The Quantitative Assessment of the Secreted IgG Repertoire after Recall to Evaluate the Quality of Immunizations

“…Although simple and robust, titer measurements represent an average of the present IgG repertoire. Moreover, Ab titer only partly correlates with protection, even for Ab-mediated vaccines (13). Indeed, this measure is not suitable to resolve the full complexity of the humoral response in terms of biochemical (.10 3 different Abs in serum) (14), biophysical (affinity, specificity), or temporal dimensions (long half-lives, large distribution volume) (15,16).…”

Hypogammaglobulinemia in children: a warning sign to look deeply?

“…Transitional B cells, considered an intermediate state between immature and mature B cells with reduced proliferative and functional capabilities were also studied. Piatosa et al reported increased number of transitional B cells associated with granuloma formation and enteropathy in children with CVID, and others have shown increased relative frequencies in children aged from 24 to 60 months with unspecific hypogammaglobulinemia . The increased number of transitional B cells in UH group may reflect a more activated status of the immune response in children with hypogammaglobulinemia without serious complications.…”

“… Figure S1. (A) Facs gating strategy to analyze B cells (CD19 + ) and B‐cell subsets : naive (N): CD27 − IgD + ; non‐switched memory (NS): CD27 + IgD + ; switched memory (SW): CD27 + IgD − , atypical (A): CD27 + IgD − ; CD21 low , transitional (TR): CD38 ++ IgM ++ , plasmablast (PB): CD38 ++ IgM − and CD24 hi CD38 hi B cells; (B) CD4 + and CD8 + T‐cell subset, effector cells (Eff): CCR7 − CD45RA + , naive (N): CCR7 + CD45RA + , central memory (CM): CCR7 + CD45RA − and effector memory (Em): CCR7 − CD45RA − .…”