SUMMARY
1. Selective IgA deficiency is defined as the isolated undetectable serum IgA (with normal IgG and IgM levels) in a patient older than 4 years of age. IgA deficiency is the most common primary immunodeficiency in humans with a prevalence of up to 1:400 in the caucasian population.
2. IgA is normally concentrated in mucosal secretions (pulmonary secretions, saliva, tears, breast milk, GI secretions) while its concentration in the serum is relatively low. The IgA functions in mucosal immunity by preventing the attachment of microorganisms to body surfaces. Microorganisms are destroyed by neutrophils and macrophages which recognize the Fc portion of bound IgA.
3. The majority of patients (two-thirds) with selective IgA deficiency are healthy and asymptomatic. These patients do not require any treatment and do not require regular follow up.
4. A minority of patients with IgA deficiency are characterized by the following clinical features.
•Sinopulmonary Infections - Recurrent ear infections, sinus infections, and pneumonias with encapsulated bacteria are the
most common infectious complications reported. Patients with concurrent IgG subclass deficiency (especially IgG2) more commonly have these types of
infections.
•Autoimmune Disorders This may represent the most common disease feature of IgA deficiency. Conditions r eported include ITP, autoimmune hemolytic anemia, rheumatoid arthritis, SLE, thyroiditis, and vitiligo.
•Gastrointestinal Disorders These include giardiasis, nodular lymphoid hyperplasia, celiac disease, and inflammatory bowel
disease.
•Allergic Disease Conditions such as asthma, allergic rhinitis,
atopic dermatitis, and food allergy are common in IgA deficiency.
5. Very rarely, anaphylactic transfusion reactions to plasma-containing blood products may occur. These patients should be tested for anti-IgA antibodies.
6. In rare cases, patients with selective IgA deficiency may progress to Common Variable Immune Deficiency (CVID). Thus, patients who are symptomatic with sinopulmonary infections should be followed longitudinally to determine if CVID (low IgG and impaired antibody response) develops.
7. The diagnosis of selective IgA deficiency requires the demonstration of undetectable IgA levels with normal IgG and IgM levels. Determination of specific antibody responses to vaccines is recommended in patients with sinopulmonary infections to rule out concurrent specific antibody deficiency.
8. For patients with recurrent bacterial infections, prophylactic antibiotic therapy may be utilized. Immunoglobulin replacement therapy is generally not indicated for selective IgA deficiency alone (IVIG contains minimal IgA).
OVERVIEW
Selective IgA deficiency is defined as the isolated undetectable serum IgA (with normal IgG and IgM levels) in a patient older than 4 years of age. IgA deficiency is the most common primary immunodeficiency in humans with a prevalence of up to 1:400 in the population.
IgA is normally concentrated in mucosal secretions (pulmonary secretions, saliva, tears, breast milk, GI secretions) while its concentration in the serum is relatively low. The IgA functions in mucosal immunity by preventing the attachment of microorganisms to body surfaces. Microorganisms are destroyed by neutrophils and macrophages which recognize the Fc portion of bound IgA.
The majority of patients (two-thirds) with selective IgA deficiency are healthy and asymptomatic. These patients do not require any treatment and do not require regular follow up.
A minority of patients with IgA deficiency are characterized by the following clinical features.
•Sinopulmonary Infections - Recurrent ear infections, sinus infections, and pneumonias
with encapsulated bacteria are the most common infectious complications reported.
Patients with concurrent IgG subclass deficiency (especially IgG2) more commonly
have these types of infections.
•Autoimmune Disorders This may represent the most common disease feature of IgA
deficiency. Conditions reported include ITP, autoimmune hemolytic anemia, rheumatoid
arthritis, SLE, thyroiditis, and vitiligo.
•Gastrointestinal Disorders These include giardiasis, nodular lymphoid hyperplasia,
celiac disease, and inflammatory bowel disease.
•Allergic Disease Conditions such as asthma, allergic rhinitis, atopic dermatitis, and food
allergy are common in IgA deficiency.
Very rarely anaphylactic transfusion reactions to plasma-containing blood products may occur. These patients should be tested for anti-IgA antibodies.
Some patients with selective IgA deficiency may progress to Common Variable Immune Deficiency (CVID). Thus, patients who are symptomatic with sinopulmonary infections should be followed longitudinally to determine if CVID develops.
EVALUATION
It should be noted that the diagnosis of IgA deficiency cannot be made in children younger than 4yo (low IgA levels can be normal in this age group).
Step 1: Immune Evaluation
Quantitative immunoglobulins (IgG, IgM, IgA)
Antibody titers to vaccine antigens
In selective IgA deficiency, the IgA is undetectable but the IgG and IgM
levels are normal.
Protein (Tetanus, Diptheria) and polysaccharide (Pneumococcus)
vaccine antibody response should be evaluated. If these antibody levels
are low, patients should be revaccinated and repeat levels should
checked in 4-6 weeks. Vaccine responses are typically normal in selective
IgA deficiency.
MANAGEMENT
The addition of prophylactic antibiotics can be considered in certain patients who continue to have infections despite appropriate treatment of contributing conditions such as allergic rhinitis. Two sample prophylaxis regimens are outlined below:
1. Amoxicillin 20mg/kg divided twice daily. Maximum of 500mg
twice daily.
2. Azithromycin 10mg/kg once weekly. Maximum of 1 gram once
weekly.
RESOURCES
Diagnostic Resources
1. *IBT - Anti-IgA Antibody Levels
Literature Resources
1. Yel 2010
IgA Deficiency
2. Cunningham-Rundles 2001
IgA Deficiency
3. Aghamohammadi 2008
Progression of IgA deficiency to CVID