| H00088 | |
| H number | H00088 |
| Name | Common variable immunodeficiency |
| Description | There are three major categories of antibody deficiencies: (a) defects in early B cell development, (b) hyper-IgM syndromes (also called class switch recombination defects), and (c) common variable immunodeficiency (CVID). Category (c) CVID, also called acquired hypogammaglobulinemia, adult-onset hypogammaglobulinemia, or dysgammaglobulinemia, is a heterogeneous group of disorders involving both B-cell and T-cell immune function, the predominant manifestation of which is hypogammaglobulinemia. CVID is characterized by recurrent bacterial infections, decreased serum Ig levels, and abnormal antibody responses. The mutated genes that produce the CVID phenotype are known only for a minority of patients, and they are diverse in their influence on immune function. Homozygous mutations in ICOS are clearly the cause of disease. Heterozygous mutations in the TNF receptor family member TACI (transmembrane activator and calcium-modulating cyclophilin ligand interactor) can be found in up to 10% of patients with CVID. |
| Category | Immune system disease |
| Network | nt06530(H00088) PI3K signaling |
| Gene | (CVID1) ICOS [HSA:29851] [KO:K06713] (CVID2) TNFRSF13B [HSA:23495] [KO:K05150] (CVID3) CD19 [HSA:930] [KO:K06465] (CVID4) TNFRSF13C [HSA:115650] [KO:K05151] (CVID5) MS4A1 [HSA:931] [KO:K06466] (CVID6) CD81 [HSA:975] [KO:K06508] (CVID7) CR2 [HSA:1380] [KO:K04012] (CVID8) LRBA [HSA:987] [KO:K24181] (CVID10) NFKB2 [HSA:4791] [KO:K04469] (CVID11) IL21 [HSA:59067] [KO:K05434] (CVID12) NFKB1 [HSA:4790] [KO:K02580] (CVID13) IKZF1 [HSA:10320] [KO:K09220] (CVID14) IRF2BP2 [HSA:359948] [KO:K22383] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| Other DBs | ICD-11: 4A01.0Z ICD-10: D80 MeSH: D017074 OMIM: 607594 240500 613493 613494 613495 613496 614699 614700 615577 615767 616576 616873 617765 |
| Reference | PMID:18424339 AUTHORS Morra M, Geigenmuller U, Curran J, Rainville IR, Brennan T, Curtis J, Reichert V, Hovhannisyan H, Majzoub J, Miller DT. TITLE Genetic diagnosis of primary immune deficiencies. JOURNAL Immunol Allergy Clin North Am 28:387-412, x (2008) DOI:10.1016/j.iac.2008.01.004 PMID:17952897 AUTHORS Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarstrom L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J. TITLE Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee. JOURNAL J Allergy Clin Immunol 120:776-94 (2007) DOI:10.1016/j.jaci.2007.08.053 PMID:22236429 AUTHORS Park JH, Resnick ES, Cunningham-Rundles C TITLE Perspectives on common variable immune deficiency. JOURNAL Ann N Y Acad Sci 1246:41-9 (2011) DOI:10.1111/j.1749-6632.2011.06338.x PMID:12577056 (CVID1) AUTHORS Grimbacher B, Hutloff A, Schlesier M, Glocker E, Warnatz K, Drager R, Eibel H, Fischer B, Schaffer AA, Mages HW, Kroczek RA, Peter HH TITLE Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. JOURNAL Nat Immunol 4:261-8 (2003) DOI:10.1038/ni902 PMID:16007086 (CVID2) AUTHORS Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS TITLE TACI is mutant in common variable immunodeficiency and IgA deficiency. JOURNAL Nat Genet 37:829-34 (2005) DOI:10.1038/ng1601 PMID:16672701 (CVID3) AUTHORS van Zelm MC, Reisli I, van der Burg M, Castano D, van Noesel CJ, van Tol MJ, Woellner C, Grimbacher B, Patino PJ, van Dongen JJ, Franco JL TITLE An antibody-deficiency syndrome due to mutations in the CD19 gene. JOURNAL N Engl J Med 354:1901-12 (2006) DOI:10.1056/NEJMoa051568 PMID:19666484 (CVID4) AUTHORS Warnatz K, Salzer U, Rizzi M, Fischer B, Gutenberger S, Bohm J, Kienzler AK, Pan-Hammarstrom Q, Hammarstrom L, Rakhmanov M, Schlesier M, Grimbacher B, Peter HH, Eibel H TITLE B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. JOURNAL Proc Natl Acad Sci U S A 106:13945-50 (2009) DOI:10.1073/pnas.0903543106 PMID:20038800 (CVID5) AUTHORS Kuijpers TW, Bende RJ, Baars PA, Grummels A, Derks IA, Dolman KM, Beaumont T, Tedder TF, van Noesel CJ, Eldering E, van Lier RA TITLE CD20 deficiency in humans results in impaired T cell-independent antibody responses. JOURNAL J Clin Invest 120:214-22 (2010) DOI:10.1172/JCI40231 PMID:20237408 (CVID6) AUTHORS van Zelm MC, Smet J, Adams B, Mascart F, Schandene L, Janssen F, Ferster A, Kuo CC, Levy S, van Dongen JJ, van der Burg M TITLE CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. JOURNAL J Clin Invest 120:1265-74 (2010) DOI:10.1172/JCI39748 PMID:22035880 (CVID7) AUTHORS Thiel J, Kimmig L, Salzer U, Grudzien M, Lebrecht D, Hagena T, Draeger R, Voelxen N, Bergbreiter A, Jennings S, Gutenberger S, Aichem A, Illges H, Hannan JP, Kienzler AK, Rizzi M, Eibel H, Peter HH, Warnatz K, Grimbacher B, Rump JA, Schlesier M TITLE Genetic CD21 deficiency is associated with hypogammaglobulinemia. JOURNAL J Allergy Clin Immunol 129:801-810.e6 (2012) DOI:10.1016/j.jaci.2011.09.027 PMID:25468195 (CVID8) AUTHORS Charbonnier LM, Janssen E, Chou J, Ohsumi TK, Keles S, Hsu JT, Massaad MJ, Garcia-Lloret M, Hanna-Wakim R, Dbaibo G, Alangari AA, Alsultan A, Al-Zahrani D, Geha RS, Chatila TA TITLE Regulatory T-cell deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like disorder caused by loss-of-function mutations in LRBA. JOURNAL J Allergy Clin Immunol 135:217-27 (2015) DOI:10.1016/j.jaci.2014.10.019 PMID:24140114 (CVID10) AUTHORS Chen K, Coonrod EM, Kumanovics A, Franks ZF, Durtschi JD, Margraf RL, Wu W, Heikal NM, Augustine NH, Ridge PG, Hill HR, Jorde LB, Weyrich AS, Zimmerman GA, Gundlapalli AV, Bohnsack JF, Voelkerding KV TITLE Germline mutations in NFKB2 implicate the noncanonical NF-kappaB pathway in the pathogenesis of common variable immunodeficiency. JOURNAL Am J Hum Genet 93:812-24 (2013) DOI:10.1016/j.ajhg.2013.09.009 PMID:24746753 (CVID11) AUTHORS Salzer E, Kansu A, Sic H, Majek P, Ikinciogullari A, Dogu FE, Prengemann NK, Santos-Valente E, Pickl WF, Bilic I, Ban SA, Kuloglu Z, Demir AM, Ensari A, Colinge J, Rizzi M, Eibel H, Boztug K TITLE Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency. JOURNAL J Allergy Clin Immunol 133:1651-9.e12 (2014) DOI:10.1016/j.jaci.2014.02.034 PMID:26279205 (CVID12) AUTHORS Fliegauf M, Bryant VL, Frede N, Slade C, Woon ST, Lehnert K, Winzer S, Bulashevska A, Scerri T, Leung E, Jordan A, Keller B, de Vries E, Cao H, Yang F, Schaffer AA, Warnatz K, Browett P, Douglass J, Ameratunga RV, van der Meer JW, Grimbacher B TITLE Haploinsufficiency of the NF-kappaB1 Subunit p50 in Common Variable Immunodeficiency. JOURNAL Am J Hum Genet 97:389-403 (2015) DOI:10.1016/j.ajhg.2015.07.008 PMID:21548011 (CVID13) AUTHORS Goldman FD, Gurel Z, Al-Zubeidi D, Fried AJ, Icardi M, Song C, Dovat S TITLE Congenital pancytopenia and absence of B lymphocytes in a neonate with a mutation in the Ikaros gene. JOURNAL Pediatr Blood Cancer 58:591-7 (2012) DOI:10.1002/pbc.23160 PMID:27016798 (CVID14) AUTHORS Keller MD, Pandey R, Li D, Glessner J, Tian L, Henrickson SE, Chinn IK, Monaco-Shawver L, Heimall J, Hou C, Otieno FG, Jyonouchi S, Calabrese L, van Montfrans J, Orange JS, Hakonarson H TITLE Mutation in IRF2BP2 is responsible for a familial form of common variable immunodeficiency disorder. JOURNAL J Allergy Clin Immunol 138:544-550.e4 (2016) DOI:10.1016/j.jaci.2016.01.018 |