Specialty hematology ICD-9-CM 279.01 DiseasesDB 29569 | ICD-10 D80.2 OMIM 137100 MedlinePlus 001476 | |
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Selective immunoglobulin A (IgA) deficiency (SIgAD) is a genetic immunodeficiency, a type of hypogammaglobulinemia. People with this deficiency lack immunoglobulin A (IgA), a type of antibody that protects against infections of the mucous membranes lining the mouth, airways, and digestive tract. It is defined as an undetectable serum IgA level in the presence of normal serum levels of IgG and IgM, in persons older than 4 years. It is the most common of the primary antibody deficiencies. Most such persons remain healthy throughout their lives and are never diagnosed.
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Signs and symptoms
‘85–90% of IgA-deficient individuals are asymptomatic’, although the reason for lack of symptoms is relatively unknown and continues to be a topic of interest and controversy. ‘Some patients with IgA deficiency have a tendency to develop recurrent sinopulmonary infections, gastrointestinal infections and disorders, allergies, autoimmune conditions, and malignancies’. These infections are generally mild and would not usually lead to an in-depth workup except when unusually frequent. They may present with severe reactions including anaphylaxis to blood transfusions or intravenous immunoglobulin due to the presence of IgA in these blood products. Patients have an increased susceptibility to pneumonia and recurrent episodes of other respiratory infections and a higher risk of developing autoimmune diseases in middle age.
Although it has some similarities to common variable immunodeficiency (CVID), it does not present the same lymphocyte subpopulation abnormalities. It may anyway progress to CVID.
Those patients with selective immunoglobulin A deficiency may be prone to recurrent infections when on hemodialysis.
Diagnosis
When suspected, the diagnosis can be confirmed by laboratory measurement of IgA level in the blood. SigAD is an IgA level < 7 mg/dL with normal IgG and IgM levels (reference range 70–400 mg/dl for adults; children somewhat less).
Cause
Selective IgA deficiency is inherited and has been associated with differences in chromosomes 18, 14 and 6. The afflicted person usually has no other family members with the disorder.
Pathophysiology
Pathogenesis of IgA Deficiency
‘In IgA-deficient patients, the common finding is a maturation defect in B cells to produce IgA’. ‘In IgA deficiency, B cells express IgA; however, they are of immature phenotype with the coexpression of IgM and IgD, and they cannot fully develop into IgA-secreting plasma cells’. There is an inherited inability to produce immunoglobulin A (IgA), a part of the body's defenses against infection at the body's surfaces (mainly the surfaces of the respiratory and digestive systems). As a result, bacteria at these locations are somewhat more able to cause disease.
Types include:
Treatment
The treatment consists of identification of comorbid conditions, preventive measures to reduce the risk of infection, and prompt and effective treatment of infections. Infections in an IgA-deficient person are treated as usual (i.e., with antibiotics). There is no treatment for the underlying disorder.
Use of IVIG as treatment
There is a historical popularity in using intravenous immunoglobulin (IVIG) to treat SIGAD, but the consensus is that there is no evidence that IVIG treats this condition. In cases where a patient presents SIGAD and another condition which is treatable with IVIG, then a physician may treat the other condition with IVIG. The use of IVIG to treat SIGAD without first demonstrating an impairment of specific antibody formation is extremely controversial.
Prognosis
Prognosis is excellent, although there is an association with autoimmune disease. Of note, selective IgA deficiency can complicate the diagnosis of one such condition, celiac disease, as the deficiency masks the high levels of certain IgA antibodies usually seen in celiac disease.
As opposed to the related condition CVID, selective IgA deficiency is not associated with an increased risk of cancer.
Epidemiology
Prevalence varies by population, but is on the order of 1 in 100 to 1 in 1000 people, making it relatively common for a genetic disease. SigAD occurs in 1 of 39 to 57 patients with celiac disease. This is much higher than the prevalence of selective IgA deficiency in the general population. It is also significantly more common in those with type 1 diabetes.
It is more common in males than in females.