Selective immunoglobulin A deficiency
|Selective immunoglobulin A deficiency|
The dimeric IgA molecule. 1 H-chain, 2 L-chain, 3 J-chain, 4 secretory component
|Classification and external resources|
Selective immunoglobulin A (IgA) deficiency (SIgAD) is a genetic immunodeficiency. 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. It is the most common of the primary antibody deficiencies.
Prevalence varies by population, but is on the order of up to 1 in 333 people, making it relatively common for a genetic disease.
It is more common in males than in females.
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.
|IGAD1||137100||Unknown; MSH5 suggested||6p21|
Symptoms and diagnosis
‘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. When suspected, the diagnosis can be confirmed by laboratory measurement of IgA level in the blood. 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.
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 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. Selective IgA deficiency 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, which is estimated to be approximately 1 in 400 to 18 500, depending on ethnic background. The prevalence of celiac disease in patients with selective IgA deficiency ranges from 10% to 30%, depending on the evaluated population.
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- Online 'Mendelian Inheritance in Man' (OMIM) 137100
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