Selective immunoglobulin A is a relatively mild genetic immunodeficiency.
Prevalence in Caucasian populations is approximately 1 in 500, though it is much less common in Asian populations.
Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency, defined as a serum IgA level <7 mg/dL (0.07 g/L) in individuals older than 4 years with normal IgG and IgM levels, after exclusion of other causes of hypogammaglobulinemia.
IgA deficiency is usually an incidental laboratory finding and most patients are asymptomatic.
The underlying defect involves impaired terminal differentiation of B lymphocytes into IgA-secreting plasma cells, with normal IgA genes.
Iimmunoglobulin A (IgA) antibody protects against infections of the mucous membranes of the mouth, airways, and digestive tract.
Causes: Usually idiopathic. Can be genetic (associated with HLA region variants) or secondary to drugs like phenytoin or sulfasalazine.
Defined as an undetectable serum IgA level in the presence of normal serum levels of IgG and IgM.
More common in males than in females.
Patients with selective IgA deficiency are usually asymptomatic, but can have increased frequency of infections, particularly in the respiratory, digestive and genitourinary systems.
Those who do have symptoms typically experience recurrent sinopulmonary infections (otitis media, sinusitis, pneumonia), GI issues (diarrhea, association with celiac disease and IBD), and allergic/autoimmune conditions (higher rates of rheumatoid arthritis, lupus, thyroid disease).
A selective deficiency of immunoglobulin A (IgA), the antibody that protects mucosal surfaces — particularly in the gut, respiratory tract, and saliva.
Infections are generally mild.
May be associated with severe reactions including anaphylaxis to blood transfusions or intravenous immunoglobulin due to the presence of IgA in these blood products.
Diagnosis confirmed by laboratory measurement of IgA level in the blood.
Increased susceptibility to pneumonia and recurrent episodes of other respiratory infections and a higher risk of developing autoimmune diseases in middle age.
Similar to common variable immunodeficiency, but it does not have the same lymphocyte subpopulation abnormalities.
Patients may be susceptible to recurrent infections when on hemodialysis.[8]
Associated with autoimmune disease.
Not associated with increased risk of malignancy.
Up to 10% of IgA deficiency patients have Celiac disease.
3-5% of Celiac patients are IgA deficient.
There is no treatment for the underlying disorder.
Several genetic associations have been identified: mutations in TNFRSF13B (encoding TACI), HLA-related genes, and epigenetic factors, though the exact pathogenesis remains incompletely understood.
The majority of affected individuals are asymptomatic: longitudinal data suggest up to 80% of identified patients may eventually develop symptoms.[
Recurrent sinopulmonary infections (sinusitis, pneumonia) are the most common symptomatic presentation.
Gastrointestinal infections and disorders, including a well-established association with celiac disease.
Allergic/atopic diseases-eczema, allergic rhinitis, asthma, and urticaria.
Autoimmune diseases-strong associations with SLE, thyroid disease, type 1 diabetes, inflammatory bowel disease, rheumatoid arthritis, and juvenile idiopathic arthritis; weaker associations with celiac disease, autoimmune hepatitis, and ITP.
Malignancy reported but less well characterized.
Infections tend to be more severe when SIgAD coexists with IgG subclass deficiency (particularly IgG2 or IgG4) or specific antibody deficiency.
Diagnosis
Diagnosis requires serum IgA <7 mg/dL with normal IgG and IgM in patients >4 years of age, after excluding secondary causes such as drugs, infections,
Patients with IgA levels below normal but >7 mg/dL are classified as having partial IgA deficiency, which may carry a similar clinical profile in symptomatic children.
Importantly, SIgAD can rarely progress to common variable immunodeficiency (CVID), and ongoing monitoring is recommended.
Management
There is no specific curative treatment for IgA deficiency and management is supportive:
Prophylactic or therapeutic antibiotics for recurrent infections.
Prompt antibiotics for infections, screening for associated conditions (celiac, autoimmune), and IgA-deficient blood products if transfusion is needed. IVIG is generally not used as it contains minimal IgA and won’t help mucosal immunity.
Immunoglobulin replacement therapy is generally not indicated, but may be considered in patients with concurrent IgG subclass or specific antibody deficiency using IgA-depleted products to minimize anaphylactic risk
Screening for associated conditions, particularly celiac disease (using IgG-based serologies, as IgA-based tests will be falsely negative and autoimmune diseases.
A proportion of IgA-deficient patients develop anti-IgA antibodies, which can cause severe anaphylactic transfusion reactions.
Washed cellular products or IgA-deficient donor blood should be used when possible.
Long-term monitoring for complications, progression to CVID, and development of autoimmune or allergic disease.
Prognosis: Most do well. A small subset (~20%) progress to common variable immunodeficiency (CVID), so periodic monitoring of immunoglobulin levels is reasonable.