Immunoglobulin A Deficiency

Descriptive text is not available for this imageBASICS

DESCRIPTION

  • Selective immunoglobulin A deficiency (sIgAD) is the most common primary antibody deficiency.
  • Definition:
    • sIgAD: serum immunoglobulin A (IgA) <7 mg/dL and a normal serum IgG and IgM in patients >4 years of age when other causes of hypogammaglobulinemia have been excluded
    • Partial IgA deficiency: serum IgA >7 mg/dL, but 2 standard deviations below normal for age
  • Most patients with sIgAD are asymptomatic, but some can present with recurrent infections, allergies, or autoimmune disorders.

EPIDEMIOLOGY

  • Worldwide prevalence for sIgAD is estimated to be around 1 in 700 individuals.
  • Prevalence is highest in Caucasians and lowest in Asian populations.

RISK FACTORS

Genetics

  • Cases of sIgAD are mostly sporadic, but about 20% exhibit patterns of familial inheritance.
  • Exact pattern of inheritance remains unclear; observed genetic associations include the following:
    • Partial deletions in the long or short arm and ring forms of chromosome 18 and 17p11.2 deletions
    • The presence of the 8.1 haplotype (HLA-A1, B8, DR3, DQ2), B14, DR7, DQ2, DR1, DQ5
    • Non–major histocompatibility complex (MHC)-associated genes involved in autoimmunity, including IFIH1 on chromosome 2q24 and CLEC16A on chromosome 16
  • sIgAD has also been observed more frequently in patients who have a family history of common variable immunodeficiency (CVID), which is a polygenic disorder characterized by low IgG and either low IgA or IgM
    • This suggests that there are shared genetic defects that may predispose individuals to sIgAD and CVID.
    • Some patients with sIgAD may progress to CVID.

PATHOPHYSIOLOGY

  • Unknown, may be due to several different mechanisms resulting in defects in production or secretion of IgA
  • In asymptomatic patients, absence of IgA may be partially compensated by IgM, IgG, and other components of the immune system.
  • IgA is secreted at mucosal surfaces, primarily in the respiratory and gastrointestinal (GI) tracts. Absence of IgA may increase susceptibility to infections at these sites.

COMMONLY ASSOCIATED CONDITIONS

Increased association with the following:

  • Atopy
  • Recurrent sinopulmonary infections
  • GI infections (especially Giardia lamblia)
  • GI disease:
    • Celiac disease most common, incidence of 2–3% in patients with IgA deficiency
    • Inflammatory bowel disease (Crohn disease and ulcerative colitis)
  • Autoimmune disorders
    • Systemic lupus erythematosus
    • Juvenile idiopathic arthritis, rheumatoid arthritis
    • Immune endocrinopathies (e.g., Graves disease, type 1 diabetes)
    • Autoimmune hematologic conditions
  • Nodular lymphoid hyperplasia
  • Malignancy, particularly adenocarcinoma of stomach and lymphoma usually of B cell origin

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