Selective Deficiency of Taci-Related Immunoglobulin A D80.2

Immunoglobulin A (IgA) deficiency-2 (IGAD2) is caused by a heterozygous, homozygous, or compound heterozygous mutation in the TNFRSF13B gene (604907), which encodes transmembrane activator and CAML interactor (TACI) on chromosome 17p11.2. A mutation in the TNFRSF13B gene can also cause common variable immunodeficiency-2(CVID2; 240500). The umbrella term "common variable immunodeficiency" (CVID) refers to a group of diseases characterized by deficiency of all Ig isotypes.

Selective immunoglobulin A deficiency (IGAD) is the most common form of primary immunodeficiency, with an incidence of approximately 1 in 600 individuals in the Western world (Cunningham-Rundles, 2001).

IGAD and CVID can coexist in families. Some individuals initially exhibit IGAD and then develop CVID. These observations suggest that some cases of IGAD and CVID may share a common etiology (Castigli et al. 2005).

In studying cohorts of immunodeficient individuals from Europe (162 individuals with CVID) and the United States (19 individuals with CVID and 16 with IGAD), Salzer et al. (2005) and Castigli et al. (2005) found that mutations in the TNFRSF13B gene (604907), which encodes the transmembrane activator and CAML interactor (TACI), are associated with both familial and sporadic forms of the disease. Martin and Dixit (2005) noted that 3 of the 6 mutations were found in both cohorts and occurred in both familial and sporadic cases, suggesting that a small number of common mutations may be responsible for most TACI-associated immunodeficiency cases.

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