Nature Genetics
37, 829 - 834 (2005)
Published online: 10 July 2005; | doi:10.1038/ng1601
TACI is mutant in common variable immunodeficiency and IgA deficiencyEmanuela Castigli, Stephen A Wilson, Lilit Garibyan, Rima Rachid, Francisco Bonilla, Lynda Schneider
& Raif S Geha
Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts
02115, USA.
Correspondence should be addressed to Raif S Geha raif.geha@childrens.harvard.edu The tumor necrosis factor receptor family member TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) mediates isotype switching in B cells. We found that 4 of 19 unrelated individuals with common variable immunodeficiency (CVID) and 1 of 16 individuals with IgA deficiency (IgAD) had a missense mutation in one allele of TNFRSF13B (encoding TACI). One of the four individuals with CVID had a single nucleotide insertion in the other TNFRSF13B allele. None of these mutations were present in 50 healthy subjects. TNFRSF13B mutations cosegregated with the phenotype of CVID or IgAD in family members of four index individuals that we studied. B cells from individuals with TACI mutations expressed TACI but did not produce IgG and IgA in response to the TACI ligand APRIL, probably reflecting impaired isotype switching. These results suggest that TACI mutations can result in CVID and IgAD.
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