TACI, isotype switching, CVID and IgAD.
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.
Castigli
Emanuela
E
Division of Immunology, Children's Hospital, Department of Pediatrics, Harvard Medical School, One Blackfan Circle, Boston, MA 02115, USA. emanuela.castigli@childrens.harvard.edu
Geha
Raif S
RS
D053264:B-Cell Activating Factor / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000628:therapy; D006801:Humans; D017098:IgA Deficiency / Q000235:genetics*; D017578:Immunoglobulin Class Switching; D007132:Immunoglobulin Isotypes / Q000235:genetics*; D009154:Mutation; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics* / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D007132:Immunoglobulin Isotypes; C108467:TNFRSF13B protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13