(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.
The inheritance pattern is unknown, but having a family member with selective IgA deficiency increases the risk by about 50 times.
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.
Drugs such as phenytoin, sulfasalazine, gold, and D-penicillamine may lead to IgA deficiency in some patients.
Symptoms and Signs
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
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 drugs that lead to IgA deficiency.
Diagnosis is confirmed by a serum IgA level < 7 mg/dL (< 70 mg/L) with normal IgG and IgM levels and normal antibody titers in response to vaccine antigens.
Testing of family members is not recommended because most patients with low IgA have no clinically significant manifestations.
Prognosis
Treatment
Allergic manifestations are treated. Antibiotics are given as needed for bacterial infections of the ears, sinuses, lungs, or gastrointestinal or genitourinary tracts and, in severe cases, are given prophylactically.
Blood products that contain IgA are avoided 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. Most immunoglobulin replacement products on the market today have minimal amounts of IgA content and do not result in adverse events even in a patient lacking IgA.
Because immune globulin replacement therapy contains mostly IgG, patients with IgA deficiency do not benefit from it; also, anaphylactic reactions are a risk because patients may have developed anti-IgA antibodies. Rarely, if patients have no antibody response to vaccines and if prophylactic antibiotics are ineffective, specially formulated immune globulin preparations that contain extremely low levels of IgA can be tried and may be somewhat effective. If other blood components are needed, they should be IgA-deficient and washed.
Patients with selective IgA deficiency are advised to wear an identification bracelet to prevent inadvertent plasma or immune globulin administration, which could lead to anaphylaxis.
Key Points
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Selective IgA deficiency is the most common primary immunodeficiency.
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Patients may be asymptomatic or have recurrent infections or autoimmune disorders; some develop CVID over time, but in others, selective IgA deficiency spontaneously resolves.
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Suspect selective IgA deficiency if patients have anaphylactic reactions to transfusions, take drugs that lead to IgA deficiency, or have recurrent infections or a suggestive family history.
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Confirm the diagnosis by measuring Ig 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.
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Give antibiotics as needed and, in severe cases, prophylactically.
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Avoid giving patients blood products or immune globulin that contain more than minimal amounts of IgA.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
immune globulin |
Gammagard S/D |
penicillamine |
CUPRIMINE |
sulfasalazine |
AZULFIDINE |
phenytoin |
DILANTIN |
