Basics
Description
Serum IgA <7 mg/dL and a normal serum IgG and IgM in patients >4 years of age
Risk Factors
Genetics
- Exact pattern of inheritance remains unclear; however, the following associations may occur:
- 22q11 deletion syndrome
- 18q syndrome
- Partial deletions in the long or short arm and ring forms of chromosome 18
- Also associated with HLA-A1, HLA-A2, B8, DR3, DQ2 (8.1), and Dw3
- Also associated with non-MHC-associated genes involved in autoimmunity including IFIH1 on chromosome 2q24, CLEC16A on chromosome 16
Pathophysiology
- Failure of B lymphocyte differentiation into plasma cells producing IgA
- Block may be due to
- Defect in T-helper cells
- Antigen-presenting cells
- B cells
- Lack of effects from various cytokines, including IL-21, IL-4, IL-6, IL-7, or IL-10
Commonly Associated Conditions
Increased association with the following:
- Atopy
- Sinopulmonary infections
- GI infections (especially Giardia lamblia)
- Inflammatory bowel disease (Crohn disease and ulcerative colitis)
- Celiac disease
- Nodular lymphoid hyperplasia
- Malignancy
- Autoimmune illnesses
- Systemic lupus erythematosus
- Immune endocrinopathies (e.g., Graves disease, type 1 diabetes)
- Autoimmune hematologic conditions
- Chronic active hepatitis
Diagnosis
History
- Patients with IgA deficiency
- Can have frequent sinopulmonary infections
- Can have frequent GI infections
- Tend to be allergic
- Have an increased incidence of autoimmune diseases
- ~30% of patients with IgA deficiency are completely healthy.
- Patients with low switched memory B cells exhibit more severe clinical features including pneumonia, autoimmune disease, and bronchiectasis.
Physical Exam
- Look for signs of recurrent infection and atopy.
- Allergies are associated with IgA deficiency. Signs include the following:
- Cobblestoning of the conjunctiva
- Allergic shiners
- Serous otitis media may be the result of recurrent ear infections or persistent fluid:
- Increased ear infections can be seen in IgA deficiency.
- Persistent fluid can be secondary to allergies.
- Pain on palpation of the sinuses
- Recurrent sinus infections are associated with IgA deficiency.
- Lung examination
- An increased frequency of pneumonia is associated with IgA deficiency.
- Swollen joints:
- An increased frequency of autoimmune disease is associated with IgA deficiency.
Diagnostic Tests & Interpretation
Diagnostic Procedures/Other
The general goal is to decide whether the patient's complaints are consistent with IgA deficiency (frequent upper respiratory and GI infections or allergies).
- Measure serum IgA level:
- If the patient is IgA deficient, exclude other conditions associated with IgA deficiency.
- Serum IgA level: Patient is considered deficient if the serum IgA level is <7 mg/dL.
- Total immunoglobulins
- If normal, helps rule out X-linked agammaglobulinemia (Bruton), common variable immunodeficiency, and severe combined immunodeficiency
- IgG subclasses:
- Helps rule out an associated IgG subclass deficiency
- Lymphocyte stimulation to mitogens
- A functional lymphocyte study
- If normal, helps rule out common variable immunodeficiency, severe combined immunodeficiency, ataxia telangiectasia, DiGeorge syndrome, and Nezelof syndrome
- Lymphocyte stimulation to Candida antigen
- No response to Candida in vivo is consistent with chronic mucocutaneous candidiasis.
- Specific antibody responses to polysaccharide and protein antigens: to evaluate for an associated specific antibody deficiency
- Screening for celiac disease
- Should include IgG antibodies against gliadin and tissue transglutaminase because IgA isotype may not be detected
Differential Diagnosis
- Toxic, environmental, drugs
- Penicillamine and anticonvulsants can induce IgA deficiency.
- Cyclosporine A has been reported to cause permanent IgA deficiency.
- Genetic/metabolic
- X-linked agammaglobulinemia (Bruton)
- Common variable immunodeficiency (CVID)
- Severe combined immunodeficiency
- Ataxia telangiectasia
- DiGeorge syndrome
- Chronic mucocutaneous candidiasis
- Nezelof syndrome
- Selective IgG2 deficiency
- Miscellaneous: Patients may be completely healthy, and IgA deficiency may be an incidental finding.
Alert
Factors that may alert you to request a referral include the following:
- Suggestion that IgA deficiency may be part of a more complex immune deficiency: An allergist/immunologist can assist with an appropriate immunologic evaluation.
- Suggestion of associated autoimmune disease: Evaluation and treatment by a rheumatologist is indicated.
- Patient likely to need a blood transfusion: An allergist/immunologist can help select appropriate blood products.
Treatment
Additional Treatment
General Measures
- There is no specific drug therapy.
- Recurrent infections should be treated aggressively with broad-spectrum antibiotics.
- Antibiotic prophylaxis to prevent recurrent sinopulmonary infections is often indicated.
- IV gammaglobulin is generally not indicated unless there is evidence of an associated specific antibody deficiency.
Alert
Patients with no detectable IgA may develop antibodies against IgA in transfused blood products. These patients are at risk for allergic reactions including anaphylactic (or anaphylactoid) transfusion reactions on subsequent exposure. It should be noted, however, that life-saving products should not be withheld in emergent situations. In the nonurgent setting, to avoid potential allergic reactions, patients may receive the following:
- Packed RBCs (only if these cells have been washed 3 times)
- Plasma products from IgA-deficient donors
- Autologous banked blood
Ongoing Care
Follow-up Recommendations
- Patients should be observed for the following:
- Sinopulmonary infections
- GI infections
- Autoimmune diseases
- Inflammatory bowel disease
- Malignancy typically of lymphoid origin
- It is important to manage infectious complications aggressively and to intervene promptly if associated conditions develop.
- It is also known that IgA deficiency may progress to CVID in some cases.
Patient Education
- IgA deficiency can be induced by some anticonvulsants and by penicillamine.
- IgA-deficient patients should wear medical alert bracelets. These patients can have anaphylaxis if administered blood products containing IgA. In an emergency situation, this is important information for the caregivers to know. However, this is not very common and does not occur with the first blood product infusion/transfusion.
Prognosis
Survival into the 7th decade is common. However it is also known that some patients may progress to CVID.
Complications
Increased incidence of the following:
- Sinopulmonary infections
- GI tract infections
- Atopy
- Autoimmune diseases
- Malignancy
Additional Reading
- Burrows PD, Cooper MD. IgA deficiency. Adv Immunol. 1997;65:245-276. [View Abstract]
- Janzi M, Kull I, Sj ¶berg R, et al. Selective IgA deficiency in early life: association to infections and allergic diseases during childhood. Clin Immunol. 2009;133(1):78-85. [View Abstract]
- Smith CA, Driscoll DA, Emanuel BS, et al. Increased prevalence of immunoglobulin A deficiency in patients with the chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Diagn Lab Immunol. 1998;5(3):415-417. [View Abstract]
- Stiehm RE. The four most common pediatric immunodeficiencies. Adv Exp Med Biol. 2007;601:15-26. [View Abstract]
- Wang N, Hammarstr ¶m L. IgA deficiency: what is new? Curr Opin Allergy Clin Immunol. 2012;12(6):602-608. [View Abstract]
- Yel L. Selective IgA deficiency. J Clin Immunol. 2010;30(1):10-16. [View Abstract]
Codes
ICD09
- 279.01 Selective IgA immunodeficiency
ICD10
- D80.2 Selective deficiency of immunoglobulin A [IgA]
SNOMED
- 29260007 Immunoglobulin A deficiency (disorder)
FAQ
- Q: Should patients with IgA deficiency be monitored for the development of progressive immunodeficiency?
- A: Patients with IgA deficiency should be monitored for progression to CVID, as this is associated with a poorer prognosis and would require treatment with IV gammaglobulin.
- Q: Should IgA-deficient patients wear medical alert bracelets?
- A: Yes. These patients can have anaphylaxis if they are given blood products containing IgA. In an emergency situation, this is important information for the caregivers to know.