TACI is mutant in common variable immunodeficiency and IgA deficiency.
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.
Castigli
Emanuela
E
Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Wilson
Stephen A
SA
Garibyan
Lilit
L
Rachid
Rima
R
Bonilla
Francisco
F
Schneider
Lynda
L
Geha
Raif S
RS
D001402:B-Lymphocytes / Q000378:metabolism; D017074:Common Variable Immunodeficiency / Q000235:genetics*; D006801:Humans; D017098:IgA Deficiency / Q000235:genetics*; D007136:Immunoglobulins / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D010641:Phenotype; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D053303:Transmembrane Activator and CAML Interactor Protein
D007136:Immunoglobulins; D008024:Ligands; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein