SUMMARY
1. Specific antibody deficiency (SAD) is characterized by normal concentrations of IgG and IgG subclasses but poor IgG antibody responses to polysaccharide antigens in patients over 2 years of age.
2. Clinically, patients develop recurrent bacterial sinopulmonary infections (otitis media, sinusitis and pneumonia). Systemic, invasive or opportunistic infections are uncommon.
3. Laboratory testing reveals normal IgG and IgG subclass levels and normal vaccine responses to protein antigens such as tetanus and diphtheria. However, patients have low or absent vaccine responses to polysaccharide antigens such as pneumococcus.
4. Patients with low pneumococcal antibody levels should receive a booster vaccination with pneumococcal polysaccharide vaccine (pneumovax 23) with responses evaluated 4-6 weeks following immunization. Normally patients should generate a response to more than half of the pneumococcal serotypes in the vaccine.
5. Pneumococcal polysaccharide vaccine should not be given to patients younger than age 2 years - polysaccharide antigen responses in this age group are unreliable.
6. Patients suffering from recurrent sinopulmonary infections may benefit from antibiotic prophylaxis (ex. amoxicillin 20mg/kg divided twice daily).
7. IVIG replacement therapy can be considered for patients who continue to have severe infections despite antibiotic prophylaxis therapy.
8. Children who have partial responses to vaccine antigens often recover over time. However, some patients may progress to develop CVID (low IgG and poor vaccine responses). Thus, immunoglobulin levels and vaccine responses should be repeated every 6-12 months.
OVERVIEW
Specific antibody deficiency (SAD) is characterized by normal concentrations of IgG and IgG subclasses but poor IgG antibody responses to polysaccharide antigens in patients over 2 years of age.
Clinically, patients develop recurrent bacterial sinopulmonary infections (otitis media, sinusitis and pneumonia). Systemic, invasive or opportunistic infections are uncommon.
Laboratory testing reveals normal IgG and IgG subclass levels and normal vaccine responses to protein antigens such as tetanus and diphtheria. However, patients have low or absent vaccine responses to polysaccharide antigens such as pneumococcus.
Children who have partial responses to vaccine antigens often recover over time, suggesting that some patients have a maturational delay in antibody responses. However, some patients may progress to develop CVID (low IgG and poor vaccine responses). Thus, immunoglobulin levels and vaccine responses should be repeated every 6-12 months.
DIFFERENTIAL DIAGNOSIS
The differential diagnosis for hypogammaglobulinemia includes the following conditions:
1. Common Variable Immune Deficiency (CVID)
2. X-lined and autosomal agammaglobulinemia
3. Hyper IgM syndromes
EVALUATION
Testing for defects in humoral immunity should be considered for patients presenting with recurrent bacterial sinopulmonary infections with encapusulated bacteria.
Step 1: Quantitative Humoral Evaluation
-Quantitative immunoglobulins (IgG, IgM, IgA)
-IgG Subclasses
-Flow cytometry for B-cell, T-cell, and NK cell numbers
-In SAD the quantitative immunoglobulin levels and IgG subclass levels are normal.
-The total B cell numbers are normal in SAD. T and NK cell numbers are also normal.
Step 2: Functional Humoral Evaluation
-Antibody titers to vaccine antigens
-Protein and polysaccharide vaccine antibodies should be measured (ex. Tetanus, Diphtheria, H. Influenzae type B, and Pneumococcus). If serum antibody titers are low, patients can be vaccinated with repeat titers drawn 4-6 weeks later.
-Antibody titers are generally normal for protein antigens (Tetanus, Diphtheria) but low for polysaccharide antigens (Pneumococcus).
MANAGEMENT
Patients who are asymptomatic do not require therapy. Antibiotic prophylaxis can be considered for patients who suffer from recurrent sinopulmonary infections. Two sample prophylaxis regimens are listed below:
Amoxicillin 20mg/kg divided twice daily. Maximum of 500mg twice daily.
Azithromycin 10mg/kg once weekly. Maximum of 1 gram once weekly.
In certain cases, IVIG replacement therapy can be considered for patients who continue to have severe infections despite antibiotic prophylaxis therapy. This therapy should not be continued indefinitely - cessation of IVIG within 1-2 years to assess endogenous antibody levels and vaccine responses is recommended.