TACI and CVID
Common variable immunodeficiency (CVID) is one of the most prevalent primary immunodeficiency syndromes, affecting approximately 1 in 25,000 (Primary immunodeficiency diseases 1999). The main immunological defect in CVID is a failure of B cells to produce immunoglobulin. This antibody deficiency predisposes patients to recurrent infections, most frequently of the respiratory tract (Yong et al. 2011). Further clinical manifestations may include autoimmunity, enteropathy, granulomatous disease, lymphoproliferation, or malignancy (Hammarstrom et al. 2000). Although generally sporadic, approximately 10% of CVID patients demonstrate familial clustering. Furthermore, it is well established that IgA deficiency (IgAD) can also occur in family members of patients with CVID (Vorechovsky et al. 2000). These observations suggested a genetic background of disease. In the past decade, a growing number of genes and mutations associated with CVID/IgAD have been identified....
- Bacchelli C, Buckland KF, Buckridge S, Salzer U, Schneider P, Thrasher AJ, Gaspar HB. The C76R transmembrane activator and calcium modulator cyclophilin ligand interactor mutation disrupts antibody production and B-cell homeostasis in heterozygous and homozygous mice. Am Acad Allergy Asthma Immunol. 2011; https://doi.org/10.1016/j.jaci.2011.02.037.CrossRefGoogle Scholar
- Banner D, D’Arcy A, Janes W, Gentz R, Schoenfeld H, Broger CL, et al. Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation. Cell Death Differ. 1993;73:431–45.Google Scholar
- Lee JJ, Jabara HH, Garibyan L, Rauter I, Sannikova T, Dillon SR, Bram R, Geha RS. The C104R mutant impairs the function of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) through haploinsufficiency. J Allergy Clin Immunol. 2010;126(6):1234–41.e2.CrossRefGoogle Scholar
- Primary immunodeficiency diseases. Report of an IUIS scientific committee. International Union of Immunological Societies. Clin Exp Immunol. 1999;118(suppl 1):1–28.Google Scholar
- Romberg N, Virdee M, Chamberlain N, Oe T, Schickel J, Perkins T, Cantaert T, Rachid R, Rosengren S, Palazzo R, Geha R, Cunningham-Rundles C, Meffre E. TNF receptor superfamily member 13b (TNFRSF13B) hemizygosity reveals transmembrane activator and CAML interactor haploinsufficiency at later stages of B-cell development. J Allergy Clin Immunol. 2015; https://doi.org/10.1016/j.jaci.
- Salzer U, Chapel HM, Webster ADB, Pan-Hammarström Q, Schmitt-Graeff A, Schlesier M, Peter HH, Rockstroh JK, Schneider P, Schäffer AA, Hammarström L, Grimbacher B. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet. 2005;37(8):820.CrossRefGoogle Scholar
- Salzer U, Bacchelli C, Buckridge S, Pan-Hammarström Q, Jennings S, Lougaris V, et al. Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes. Blood. 2009;113(9):1967–76.CrossRefGoogle Scholar
- Vorechovsky I, Cullen M, Carrington M, Hammarstrom L, Webster ADB. Fine mapping of IGAD1 in IgA deficiency and common variable immunodeficiency: identification and characterization of haplotypes shared by affected members of 101 multiple-case families. J Immunol. 2000;164:4408–16.CrossRefGoogle Scholar
- Yong FP, Thaventhiran JE, Grimbacher B. A rose is a rose but CVID is not CVID: common variable immunodeficiency (CVID), what do we know in 2011. Adv Immunol. 2011;111:46–107.Google Scholar