What causes of immunoglobulin A deficiency (IgAD)?

Updated: May 15, 2018
  • Author: Marina Y Dolina, MD; Chief Editor: Michael A Kaliner, MD  more...
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The underlying causes of most cases of this heterogeneous disease remain unknown. Familial inheritance has been recognized in 25% of affected individuals, suggesting a strong genetic influence.

  • Case reports of some affected families indicate that inheritance may be autosomal dominant or recessive. In other families in which multiple members are affected, the pattern of inheritance does not conform to strict Mendelian rules.

    • In some families, the immunodeficiency can appear to skip generations; in others, one family member in a given generation may have IgAD, while another in the same generation may have common variable immunodeficiency (CVID), suggesting variable expressivity and penetrance of disease susceptibility gene(s).

    • Recent studies have shown that susceptibility to either CVID or IgAD may be linked to specific alleles of the major histocompatibility complex, suggesting that these alleles, or alleles of closely linked genes with which they are in linkage disequilibrium, are somehow involved in the pathogenesis of CVID and IgAD.

  • IgA deficiency is a particularly notable aspect of ataxia-telangiectasia and related disorders in which mutations in DNA processing/repair mechanisms interfere with rearrangements of immunoglobulin and T-cell receptor genes. Other signs of ataxia-telangiectasia should be carefully sought in children presenting with IgAD, particularly if they also have developmental delays. These manifestations may occur before the telangiectases are obvious.

  • In his 1991 report of 2 mothers with IgAD, de Laat suggests that transplacental passage of anti-IgA antibodies can also cause IgAD in an infant by inducing excessive IgA-specific T-cell suppressor activity. [74]

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