KEGG   DISEASE: Common variable immunodeficiency
Entry
H00088                      Disease                                
Name
Common variable immunodeficiency
  Supergrp
Disorders of adaptive immunity [DS:H02526]
Primary immunodeficiency disease [DS:H01725]
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
Brite
Human diseases [BR:br08402]
 Immune system diseases
  Primary immunodeficiency
   H00088  Common variable immunodeficiency
Human diseases in ICD-11 classification [BR:br08403]
 04 Diseases of the immune system
  Primary immunodeficiencies
   4A01  Primary immunodeficiencies due to disorders of adaptive immunity
    H00088  Common variable immunodeficiency
Pathway
hsa04662  B cell receptor signaling pathway
hsa04640  Hematopoietic cell lineage
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]
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
  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
Reference
  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
Reference
  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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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

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