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Chapter: Medical Immunology: Primary Immunodeficiency Diseases

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Selective Immunoglobulin A Deficiency

IgA deficiency is the most common immunodeficiency. The frequency estimates of IgA de-ficiency vary according to the criterion used to define it and with the sensitivity of the meth-ods used to measure IgA.

Selective Immunoglobulin A Deficiency

IgA deficiency is the most common immunodeficiency. The frequency estimates of IgA de-ficiency vary according to the criterion used to define it and with the sensitivity of the meth-ods used to measure IgA. An individual is considered IgA deficient when his or her con-centration of serum IgA is below 7 mg/dL, as measured by routine methods for immunoglobulin assay (such as radial immunodiffusion or immunonephelometry). De-fined by this criterion, IgA deficiency is diagnosed with a frequency of approximately 1 out of 600–800 normal Caucasian individuals.

1. Physiopathology

 

IgA deficiency appears to be a heterogeneous entity from the pathogenic point of view. In some cases phenotypic studies of circulating B cells show patterns similar to those of cord  blood B lymphocytes, suggesting a differentiation abnormality, sometimes reflected by a defect in secretion of intracytoplasmic IgA. In other cases there is evidence for im-munoregulatory defects, such as:

·              Predominant synthesis of IgG1 and IgG3 antibodies to pneumococcal polysaccha-rides, even when the serum levels of IgG2 are normal (IgM and IgG2 are the immunoglobulin isotypes of antipolysaccharide antibodies in humans).

·              Longitudinal variations in IgA levels, which may fluctuate widely, from very low to normal and back to very low.

·              Anti-IgA antibodies reacting with isotypic or allotypic determinants of IgA can be detected in about one third of the patients, usually in low titers. However, when present in high titers ( >80 when measured by passive hemagglutination), anti-IgA antibodies can cause hypersensitivity and possibly fatal reactions upon transfusion of IgA-containing blood products. Anti-IgA antibodies may con-tribute to the perpetuation of the IgA deficiency. The administration of radio-labeled IgA to patients with anti-IgA antibodies is followed by its rapid elimi-nation from the circulation (in a matter of hours). More significantly, a comparison of the levels of residual IgA in patients with and without anti-IgA antibodies demonstrated that those with antibodies have the lowest levels.

2. Clinical Presentation

 

Most cases of IgA deficiency are asymptomatic. Patients with combined IgA and IgG2 de-ficiency may present with recurrent sinus infections caused by bacteria with polysaccharide capsules. Infections withGiardia lamblia are more frequent in patients with IgA deficiency than in individuals with normal IgA levels. As in patients with agammaglobulinemia, this parasitic infection may lead to chronic diarrhea and malabsorption.

Abnormal immune reactivity is not unusual in IgA-deficient individuals. Many IgA-deficient individuals have antibodies to food proteins, which in most cases appear to be of no consequence. But IgA deficiency can also be associated with “autoimmune” disorders such as pernicious anemia and rheumatoid arthritis.

3. Diagnosis

 

Diagnosis is based on IgA assay. A patient older than 4 years with less than 7 mg/dL of serum IgA, normal levels of IgG and IgM, with no other primary or secondary immune de-ficiency fulfills the clinical and laboratory criteria for the diagnosis of selective IgA defi-ciency. Patients with other forms of primary immune deficiency such as ataxia-telangicta-sia can also have selective IgA deficiency.

4. Therapy

 

Treatment is usually targeted to relieve symptoms, using antibiotics as needed for infec-tions and treating allergies and sinus inflammation. Replacement therapy with IVIg for IgA deficiency is not recommended, because only small amounts of IgA are present in com-mercial gamma globulins and may cause adverse reactions. Administration of intravenous gamma globulin is indicated in patients with combined IgA and IgG2 deficiency or in IgA-deficient patients who fail to produce antibodies to bacterial polysaccharides. These pa-tients should receive IVIg preparations with very low IgA content to avoid hypersensitiv-ity reactions due to IgA antibodies.

IgA antibodies should be assayed in any known IgA-deficient patient considered for elective transfusion with IgA-containing blood products. If found, the blood bank should be notified so that steps can be taken to make sure that any blood transfused to the patient is IgA-depleted or a blood product or gamma globulin preparation depleted of IgA. IgA-depleted blood transfusions can be achieved by obtaining compatible blood from a healthy IgA-deficient donor or by extensively washing red cells to remove IgA-containing plasma. Patients should be educated about their increased risk of reactions to blood products.

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