Selective IgA deficiency is an IgA level < 7 mg/dL (< 70 mg/L, < 0.4375 micromol/liter) with normal IgG and IgM levels. It is the most common primary immunodeficiency. Many patients are asymptomatic, but some develop recurrent infections and autoimmune disorders. Some patients develop common variable immunodeficiency over time, and in some it remits spontaneously. Diagnosis is by measuring serum immunoglobulins. Treatment is antibiotics as needed (sometimes prophylactically) and usually avoidance of blood products that contain IgA.
(See also Overview of Immunodeficiency Disorders and Approach to the Patient With an Immunodeficiency Disorder.)
IgA deficiency involves B cell defects. Prevalence ranges from 1/100 to 1/1000 (1).
The inheritance pattern is unknown, but having a family member with selective IgA deficiency increases the risk by approximately 50 times (2).
Some patients have mutations in the TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) gene. Selective IgA deficiency also commonly occurs in patients with certain HLA haplotypes; rare alleles or deletions of genes in the major histocompatibility complex (MHC) class III region are common.
General references
1. Palmer DS, O'Toole J, Montreuil T, et al. Screening of Canadian Blood Services donors for severe immunoglobulin A deficiency. Transfusion 2010;50(7):1524-1531. doi:10.1111/j.1537-2995.2010.02588.x
2. Vorechovský I, Zetterquist H, Paganelli R, et al. Family and linkage study of selective IgA deficiency and common variable immunodeficiency. Clin Immunol Immunopathol 1995;77(2):185-192. doi:10.1006/clin.1995.1142
Symptoms and Signs of Selective IgA Deficiency
Most patients with selective IgA deficiency are asymptomatic; others have recurrent sinopulmonary infections, diarrhea, allergies (eg, asthma, associated nasal polyps), or autoimmune disorders (eg, celiac disease, inflammatory bowel disease, systemic lupus erythematosus, chronic active hepatitis).
Anti-IgA antibodies may develop after exposure to IgA in transfusions, immune globulin (IVIG), or other blood products; rarely, if reexposed to these products, patients may have anaphylactic reactions.
Diagnosis of Selective IgA Deficiency
Measurement of serum immunoglobulin levels
Measurement of antibody response to vaccine antigens
Diagnosis of selective IgA deficiency is suspected in patients who have recurrent infections (including giardiasis); anaphylactic transfusion reactions; or a family history of common variable immunodeficiency (CVID), IgA deficiency, or autoimmune disorders or who are taking medications that lead to an acquired IgA deficiency.
Patients with suspected IgA deficiency should have immunoglobulin levels measured; diagnosis is confirmed by a serum IgA level < 7 mg/dL (< 70 mg/L, 0.4375 micromol/liter ) with normal IgG and IgM levels (1). IgG antibody titers are measured before and after administration of vaccine antigens; patients should have a normal rise in antibody titers ( ≥ 2-fold increase in titer at 2 to 3 weeks).
Testing of family members is not recommended because most patients with low IgA have no clinically significant manifestations. However, patients who have a history of transfusion-related reactions should be tested for IgA deficiency, particularly if they have a family member with IgA deficiency.
Diagnosis reference
1. Bonilla FA, Khan DA, Ballas ZK, et al: Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol 136(5):1186–205.e2078, 2015. doi:10.1016/j.jaci.2015.04.049
Treatment of Selective IgA Deficiency
Antibiotics as needed for treatment and, in severe cases, for prophylaxis
Avoidance of blood products that contain IgA
Allergic manifestations are treated. Antibiotics are given as needed for bacterial infections of the ears, sinuses, lungs, or gastrointestinal or genitourinary tracts. In severe cases, antibiotics are given prophylactically.
Because immune globulin replacement therapy contains mostly IgG and minimal amounts of IgA, patients with IgA deficiency do not benefit from it. However, there still is some risk of sensitizing patients to IgA or triggering an anaphylactic reaction in those who previously developed anti-IgA antibodies. Rarely, if patients have no antibody response to vaccines and if prophylactic antibiotics are ineffective in preventing infection, specially formulated immune globulin preparations that contain extremely low levels of IgA can be tried and may be somewhat effective.
Blood products that contain IgA are avoided in patients with IgA deficiency because IgA can elicit an anti-IgA–mediated anaphylactic reaction. If transfusion of red blood cells (RBCs) is needed, only washed packed RBCs can be used. If other blood components are needed, they should be IgA-deficient, and cellular components should be washed.
Patients with selective IgA deficiency are advised to wear medical identification to prevent inadvertent plasma or immune globulin administration, which could lead to anaphylaxis.
Prognosis for Selective IgA Deficiency
A few patients with IgA deficiency develop CVID over time; others improve spontaneously. Prognosis is worse if an autoimmune disorder develops.
Key Points
Selective IgA deficiency is the most common primary immunodeficiency.
Patients may be asymptomatic or have recurrent infections or autoimmune disorders; some develop CVID over time, but in others, selective IgA deficiency spontaneously resolves.
Suspect selective IgA deficiency if patients have anaphylactic reactions to transfusions, take medications that lead to an acquired IgA deficiency, or have recurrent infections or a suggestive family history.
Confirm the diagnosis by measuring immunoglobulin levels and antibody titers after vaccines are given; an IgA level < 7mg/dL (< 70 mg/L) and normal IgG and IgM levels and antibody titers are diagnostic.
Give antibiotics as needed and, in severe cases, prophylactically.
Avoid giving patients blood products or immune globulin that contain more than minimal amounts of IgA.
