title: Genetics of common variable immunodeficiency: role of transmembrane activator and calcium modulator and cyclophilin ligand interactor.
abstract: Common variable immunodeficiency (CVID) is the most common clinically manifested primary immunodeficiency, which represents a heterogeneous group of hypogammaglobulinemias of largely unknown molecular defects. The hallmark of the disease is the elevated susceptibility to recurrent infections of respiratory and gastrointestinal tract, mainly due to encapsulated bacteria while a significant proportion of patients with CVID develop autoimmune and lymphoproliferative complications. The primary cause of CVID is still not known. However, a number of distinct genetic defects including in inducible co-stimulator (ICOS), B-cell-activating factor receptor (BAFFR) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) have been identified in a minority of patients with CVID. Mutations in tumour necrosis factor receptor superfamily (TNFRSF) member, TACI, are more frequently found to be associated to the disease in about 10% of patients with CVID, but may require additional immunologic defects for complete expression of the phenotype, as unaffected heterozygotes have also been described. Clinically, patients with TACI mutations could present with the complete spectrum of complications seen in CVID. Recent animal studies have provided substantial information on TACI signalling, yet it still offers an outstanding opportunity for further exploration of the aetiology, as a large part of it remains poorly understood. In this review, we aim at giving an insight into the genetics underlying the CVID and particularly at outlining the role of TACI and its relative contribution to the development of CVID-like phenotypes in human.
authors.affiliation: Genetech Research Institute, Colombo, Sri Lanka.|Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo, Sri Lanka.
authors.forename: H D
authors.initials: HD
authors.lastname: Sathkumara
authors.affiliation: Medical Research Institute, Colombo, Sri Lanka.
authors.forename: N R
authors.initials: NR
authors.lastname: De Silva
authors.affiliation: Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo, Sri Lanka.
authors.forename: S
authors.initials: S
authors.lastname: Handunnetti
authors.affiliation: Genetech Research Institute, Colombo, Sri Lanka.
authors.forename: A D
authors.initials: AD
authors.lastname: De Silva
mesh_terms: D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics* / Q000276:immunology; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000235:genetics* / Q000276:immunology; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D015398:Signal Transduction; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics* / Q000276:immunology
chemical_list: D053265:B-Cell Activation Factor Receptor; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; D053303:Transmembrane Activator and CAML Interactor Protein