Background
Immunoglobulin D (IgD) deficiency is a defect of humoral immunity that is characterized by abnormally low serum levels of IgD immunoglobulins. Little is known about the normal function of IgD, and few clinical signs or symptoms are associated with its absence. Individuals with low or absent levels of IgD do not appear unusually predisposed to infections.
Pathophysiology
Genetic rearrangements occur during the maturation of B lymphocytes, eventually resulting in the surface expression of both immunoglobulin M (IgM) and IgD on mature B cells. Cell signaling occurs through this surface IgD. IgD production by B cells is stimulated by interleukin (IL)–4 and IL-10. [1]
The physiologic purpose of free serum IgD is not well understood, though it may fine tune or modulate humoral immune response. [2] In mice, IgD may substitute for some functions of IgM when IgM is absent. Studies in IgM-deficient IgM-/- mice reveal that B cells with surface expression of IgM were replaced by B cells with surface expression of IgD. Immunization of IgM-/- mice revealed an IgD immune response in place of the now absent IgM response, although with a delayed increase in antibody concentration as compared to normal. [3] Recent studies have suggested that IgD-only B cells may play a significant role in immune responses to superantigens. [4] Investigations into the evolutionary origins of IgD are also ongoing. [5, 6, 7, 8]
Low serum IgD levels are not distributed in a normal gaussian fashion. [9, 10] IgD deficiency is associated with the specific human leukocyte antigens HLA-B18, F1C30, and DR3 in a Spanish Basque population [11] and HLA-B8, SC01, DR3 in white subjects in an American study. [12] A 2008 report noted that depletion of circulating IgD+ memory B cells occurs in pediatric HIV infection, despite control of viral load with highly active anti-retroviral therapy (HAART). [13]
Epidemiology
Frequency
One report indicates that approximately 11% of 371 American Red Cross blood donors and 6% of 1529 study subjects had low or undetectable IgD levels (< 0.002 mg/mL). In the study group, a number of the individuals with low IgD had rheumatologic disease (eg, juvenile rheumatoid arthritis, lupus, psoriatic arthritis, vasculitis), but the frequency of low IgD within groups of patients with each disease did not differ from the normal controls using chi-square analysis. [10] In another study, using a cutoff of 2.15 IU/mL, assays of 245 healthy adults and 301 healthy children revealed that approximately 13% of each group had low levels of IgD. [9]
Mortality/Morbidity
Low or undetectable levels of IgD, in the absence of other concurrent disease or immune defects (eg, common variable immunodeficiency, complement deficiency), are not associated with morbidity or increased mortality. Specifically, patients with low or undetectable IgD levels do not demonstrate an increased incidence of infections of any type. [14]
Sex
Overall levels of serum IgD are higher in males than females, [15] but specific incidence of abnormally low IgD is approximately equal between the sexes. [9]
Age
Children younger than 3 years, both with and without an immunodeficiency, appear to have an increased prevalence of low IgD levels. [16, 17, 18] After infancy, age is not associated with increased prevalence of low IgD levels. [9]
Prognosis
In the absence of comorbid conditions, prognosis for immunoglobulin D (IgD) deficiency is excellent.
Patient Education
Educate patients about the humoral immune system and inform them that the specific function of immunoglobulin D (IgD) is not fully understood. Request patients to promptly report any signs or symptoms of infection to their primary care provider.
