SELECTIVE IgA DEFICIENCY
 
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SELECTIVE IgA DEFICIENCY

 

DEFINITION:

A primary immunodeficiency disorder characterized by a reduction in the production of IgA antibodies resulting in recurrent respiratory and gastrointestinal infections.

EPIDEMIOLOGY:

  • incidence: 1/400-800 (most common B cell disorder)
  • age of onset:
    • any but as early as 1 year of age
  • risk factors:
    • familial - autosomal dominant and recessive forms
      • chrom.#: ?
      • gene: ?
    • acquired - see below
    • F > M (2:1)

PATHOGENESIS:

1. Background

  • B cells differentiate into plasma cells which produce IgA1 and IgA2 which are used to protect the respiratory, gastrointestinal, and other secretory areas
  • IgA is found in two distinct forms: in the serum and in secretions (the levels of which are independently controlled)

2. Etiology

1. Hereditary Predisposition

  • autosomal recessive and dominant forms
  • increased incidence in those with:
    • first degree relatives with Common Variable Immuno-deficiency
    • HLA-B8, -DR3
    • chromosome 18 abnormalities (deletions, ring)

2. Acquired

  • congential rubella infections
  • dilantin
  • penicillamine

3. Defect

  • interference of B cell differentiation results in the production of plasma cells arrested at an immature stage of development (the cells express surface IgM, IgD, and IgA) -> population of plasma cells unable to secrete IgA1 and/or IgA2 -> serum and/or secretory IgA deficiency
  • in about 90% of cases, there is an absence of serum and secretory IgA with normal amounts of secretory component and normal T-cell function
  • selective IgA Deficiency can be found in isolation or associated with other deficiencies
    • Isolated IgA deficiency
    • IgA Deficiency + IgG subclass deficiency (IgG2, IgG3)
    • IgA Deficiency + T-cell deficiency
  • the variability in clinical manifestations (from asymptomatic to severe systemic infections) is reflected in the variable extent of IgA immunodeficiency and associated deficiencies: the clinical manifestations tend to be more severe when IgA Deficiency is associated with other deficiencies
  • autoimmunity may be due to excessive stimulation of the lymphoid system by antigenic agents normally eliminated by IgA resulting in the generation of antigen-antibody complexes

CLINICAL FEATURES:

1. Immunodeficiency Manifestations

1. Respiratory

  • chronic sinopulmonary infections (chronic cough)
    • chronic bronchitis
    • obstructive lung disease
    • recurrent pneumonias
  • seen more frequently in those with:
    • concomitant IgG2 subclass deficiency
    • atopy
    • cell-mediated immunodeficiency

2. Gastrointestinal

  • chronic diarrhea (giardiasis) +/- malabsorption

2. Complications

1. Autoimmune Disorders (in 50% of cases)

  • Rheumatoid Arthritis and SLE are the most common
  • Pulmonary Hemosiderosis, Chronic Active Hepatitis, Pernicious Anemia, Hemolytic Anemia, Thyroiditis, Idiopathic Addison's Disease, Dermatomyositis, Sjogren's Syndrome

2. Neoplasms

  • lung carcinoma
  • gastric neoplasms (carcinoma of the esophagus, colon)
  • lymphoproliferative disorders (when associated with an IgE deficiency)
  • angioimmunoblastic lymphadenopathy

3. Gastrointestinal Associations

  • Celiac Disease (with elevated IgM levels), Crohn's Disease, Intestinal Nodular Hyperplasia, Ulcerative Colitis

4. Other Associations

  • atopy (allergic disease, asthma)
  • mental retardation

INVESTIGATIONS:

1. Serum

1. Humoral-Mediated

  • reduced levels of IgA
  • reduced levels of IgE (in 50% of cases)
  • reduced levels of IgG2 (18%) and IgG4 subclasses
  • usually normal secretory component levels
  • anti-IgA antibodies (in 10%) - if found, use of fresh frozen plasma or gammaglobulin is contraindicated
  • antimilk antibodies (in 50%)
  • increased incidence of autoantibodies
  • circulating antigen-antibody complexes (in 60%)

2. Cell-Mediated

  • T-cell deficit in some forms

2. Intestinal Biopsy

  • lack of IgA-staining plasma cells

MANAGEMENT:

1. Supportive

  • treat infections - antibiotics, physiotherapy
  • direct therapy towards those diseases associated with Selective IgA Deficiency (i.e., asthma, autoimmune disorders)
  • follow for the development of autoimmune disorders and treat any that develop
  • administration of gammaglobulin, blood, or blood products is contraindicated as formation of anti-IgA antibodies may occur and may cause fatal anaphylaxis in IgA-sensitized patients
  • if possible use blood products from IgA-deficient donors, washed and packed cells, or acquired for autoinfusion
  • gammaglobulin prophylaxis has been recommended in those with combined IgA-IgG2 defects but patients should be monitered for antibodies to IgA

2. Prognosis

  • spontaneous recovery without treatment in a small number
  • those with isolated Selective IgA Deficency are usually asymptomatic or mildly affected with a normal life span
  • prognosis usually depends upon the associated diseases and the complications which may develop

 

 

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