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TACI, isotype switching, CVID and IgAD.
Immunologic Research 2007
Common Variable Immunodeficiency (CVID) is the most prevalent human primary immunodeficiency requiring medical attention. Until recently the only known genetic defect specific to CVID was ICOS deficiency that accounts for about 1% of the patients analyzed. Mutations in the TNFR family member TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor), which mediates isotype switching in B cells, were found to be present in 5% of patients with CVID. Mutations in TACI were also found in relatives of patients with CVID who suffered from IgA deficiency (IgAD) as well as in a patient with isolated IgAD. In the majority of patients described to date only one TACI allele is mutated, showing an autosomal dominant transmission of the disease. B cells from individuals with TACI mutations did not produce IgG and IgA in response to the TACI ligand, APRIL (a proliferation-inducing ligand), probably reflecting impaired isotype switching. These results suggest that TACI mutations can lead to CVID.
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