Serum IgD Levels in Children under Investigation for and with Defined Immunodeficiency

Abstract

Background: The function and regulation of circulating IgD are unclear. Serum IgD levels were increased in a wide range of immunological diseases but these associations did not give a clue to the regulation of serum IgD production. Methods: Serum IgD levels in 131 children with various non-HIV-related immunodeficiency diseases were investigated to examine their relationship with immunoglobulin or antibody production and activation of the immune system. Data from a group of 109 nonimmunodefícient children were also available for comparison. Results: There was a bimodal distribution of serum IgD levels. In 87 patients IgD levels fell below the limit of detection of 5 IU/ml, while the remainder showed an approximately normal distribution skewed to the right after log transformation. The proportion of children with undetectable IgD levels (< 5 IU/ml) was significantly increased in immunodeficient children (87/131 vs. 28/109, p < 0.001). No difference in the occurrence of immunoglobulin or antibody deficiencies was demonstrated in immunodeficient children with detectable and non-detectable IgD levels. There was a positive correlation of serum IgD with age, serum IgA and IgE, white blood count and CD4+CD25+ lymphocytes but not with other immunoglobulin isotypes or immune activation markers. Conclusion: Determination of serum IgD levels did not seem to be of particular clinical benefit in the investigation of HIV-negative immunodeficient children and serum IgD levels were not associated with the general picture of immune activation. Observed distribution patterns and associations may have implications for the regulation of serum IgD production.

Immunoglobulin D: Properties, Measurement, and Clinical Relevance

“…However, there was no correlation between the amount of IgD in serum and the amount expressed by lymphocytes (69). A positive correlation was found between serum IgD level and serum IgA and IgE levels (69), white blood cell count, and number of CD4 ϩ and CD25 ϩ lymphocytes but not with other immunoglobulin isotypes or markers of immune activation (94). Although the amount of IgD usually paralleled the amount of other immunoglobulins in serum (45), the values of IgG and IgM did not always correlate with the presence or absence of IgD, as detected by double-diffusion-in-gel assay (120).…”

“…IgD production is influenced by two major factors: an independent mechanism (only for IgD), which may be genetically determined, and also the same factors that control the production of the other immunoglobulin isotypes (94). The genes for the C region of and ␦ (C and C ␦ ) are transcribed in the same RNA (a common transcription unit) and can be expressed simultaneously.…”

“…The concentration of IgD in sera of infants and adults was age dependent (94) and showed considerable biological variation, even in people of the same age, from undetectable to 400 mg/liter (43,136). Some investigators found a linear increase of IgD until the age of 10 (66), followed by a gradual decrease until the age of 14 (50).…”

“…Since the values for serum IgD did not follow a Gaussian distribution (43), it was common to transform the results into square roots (78) or a natural logarithmic scale for statistical analysis (78,114,121). Individuals can be high or low producers of (serum) IgD (94). Early studies have suggested that about 10 to 14% of individuals had very low concentrations of serum IgD, i.e., Ͻ3 mg/liter (43,81) and that about 10% have high concentrations (Ͼ100 mg/liter).…”

“…Early studies have suggested that about 10 to 14% of individuals had very low concentrations of serum IgD, i.e., Ͻ3 mg/liter (43,81) and that about 10% have high concentrations (Ͼ100 mg/liter). It was hypothesized, but not proven (94), that low producers can convert to high producers because of infections and immune activation. Low serum IgD was not dependent on age and was not related to sex (44).…”