What is the clinical significance of Selective Immunoglobulin A (IgA) deficiency and are further investigations warranted?

From the Guidelines

IgA deficiency is a significant condition that requires investigation only in symptomatic patients, as most individuals with this deficiency remain asymptomatic throughout their lives. The pertinence of IgA deficiency lies in its association with increased risk of respiratory tract infections, gastrointestinal disorders (particularly celiac disease), autoimmune conditions, and allergic reactions including transfusion reactions 1. According to the practice parameter for the diagnosis and management of primary immunodeficiency, patients with serum IgA levels of less than 7 mg/dL and normal serum IgG and IgM levels, and in whom other causes of hypogammaglobulinemia have been excluded, should be given a diagnosis of Selective IgA Deficiency (SIGAD) 1.

Key Considerations

• Investigations should only be pursued if a patient presents with recurrent sinopulmonary infections, gastrointestinal disorders, autoimmune conditions, or allergies that suggest clinical significance 1.
• For symptomatic patients, testing should include serum immunoglobulin levels (IgA, IgG, IgM), specific antibody responses to vaccines, and potentially evaluation for associated conditions like celiac disease or other autoimmune disorders 1.
• Medication use should be investigated in patients with IgA deficiency, as certain medications can cause acquired IgA deficiency, and cessation of the drug therapy may be reversible 1.
• Patients with IgA deficiency are considered to be at risk for anaphylactic reactions to blood products, and practices vary, but some centers will transfuse products from IgA-deficient donors for IgA-deficient recipients or wash cells before they are transfused 1.

Management and Education

• Patients with SIGAD should be monitored over time for the occurrence of complications, as most affected patients with SIGAD are asymptomatic, but some do have problems over time, including respiratory and gastrointestinal tract infections, atopy, autoimmune diseases, celiac disease, and malignancy 1.
• Patients should be educated about their condition and advised to inform healthcare providers before receiving blood products to prevent potential anaphylactic reactions.
• The underlying mechanism involves a maturation defect in B cells that prevents them from producing IgA antibodies, which normally provide mucosal immunity at respiratory, gastrointestinal, and genitourinary surfaces.

From the Research

IgA Deficiency Overview

• IgA deficiency is the most common primary immunodeficiency, defined as decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes 2.
• Most individuals with IgA deficiency are asymptomatic and identified coincidentally, but some patients may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations 2.

Clinical Phenotypes Associated with Selective IgA Deficiency

• A study of 330 cases found that 56.6% of patients with IgA deficiency showed other comorbidities, including recurrent infections, allergic diseases, autoimmunity, and tumors 3.
• Recurrent ear infections, upper respiratory tract infections, and pneumonia were common in patients with selective IgA deficiency, with some developing secondary complications such as deafness, bronchiectasis, and lobectomy 3.
• Atopic disease was found in 18.78% of patients, and autoimmune manifestations were found in 11.5% of patients, including juvenile chronic arthritis, type 1 diabetes, and vitiligo 3.

Investigations and Treatment

• There is no specific treatment for selective IgA deficiency, and each patient must be managed individually 4.
• Asymptomatic subjects do not need any treatment, but it is still necessary for them to be up-to-date with vaccinations 4.
• Prophylactic antibiotics may be beneficial for patients with recurrent infections, and immunoglobulin replacement therapy should be considered in patients with selective IgA deficiency and concomitant IgG subclass deficiency 4.
• IgA- and IgM-enriched immunoglobulin replacement therapy may have potential to prevent bacterial respiratory tract infections in patients with primary immunoglobulin deficiencies 5.

Importance of Monitoring

• Close monitoring for malignancy should be strongly considered for patients with IgE deficiency, particularly those with no allergic comorbidities and those with non-common variable immunodeficiency humoral immunodeficiency 6.
• Patients with selective IgA deficiency should be monitored for the development of other immune disorders, such as IgG subclass deficiency, and for the presence of comorbidities such as atopic disease and autoimmune manifestations 3, 4.