Translational mini-review series on immunodeficiency: molecular defects in common variable immunodeficiency.
Common variable immunodeficiency (CVID) is a primary immunodeficiency that typically affects adults and is characterized by abnormalities of quantative and qualitative humoral function that are heterogeneous in their immunological profile and clinical manifestations. The recent identification of four monogenic defects that result in the CVID phenotype also demonstrates that the genetic basis of CVID is highly variable. Mutations in the genes encoding the tumour necrosis factor (TNF) superfamily receptors transmembrane activator and calcium-modulating ligand interactor (TACI) and B cell activation factor of the TNF family receptor (BAFF-R), CD19 and the co-stimulatory molecule inducible co-stimulator molecule (ICOS) all lead to CVID and illustrate the complex interplay required to co-ordinate an effective humoral immune response. The molecular mechanisms leading to the immune defect are still not understood clearly and particularly in the case of TACI, where a number of heterozygous mutations have been found in affected individuals, the molecular pathogenesis of disease requires further elucidation. Together these defects account for perhaps 10-15% of all cases of CVID and it is highly likely that further genetic defects will be identified.
Bacchelli
C
C
Molecular Immunology Unit, Institute of Child Health, London, UK.
Buckridge
S
S
Thrasher
A J
AJ
Gaspar
H B
HB
D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D053303:Transmembrane Activator and CAML Interactor Protein / Q000172:deficiency / Q000235:genetics
D018941:Antigens, CD19; D000945:Antigens, Differentiation, T-Lymphocyte; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein
Clin Immunol. 1999 Dec;93(3):190-7
10600329
Nat Genet. 2005 Aug;37(8):829-34
16007086
Annu Rev Immunol. 2000;18:393-422
10837064
Clin Exp Immunol. 2000 Jun;120(3):512-7
10844531
Eur J Immunol. 2000 Dec;30(12):3707-17
11169414
Nature. 2001 Jan 4;409(6816):97-101
11343121
Nature. 2001 Jan 4;409(6816):102-5
11343122
Nature. 2001 Jan 4;409(6816):105-9
11343123
Mol Cell Biol. 2001 Jun;21(12):4067-74
11359913
Immunity. 2001 May;14(5):573-82
11371359
Nat Immunol. 2001 Jul;2(7):638-43
11429549
Clin Exp Immunol. 2001 Jun;124(3):465-9
11472409
Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12614-9
11675497
Clin Exp Immunol. 2001 Oct;126(1):126-30
11678908
J Clin Immunol. 2001 Sep;21(5):303-9
11720003
Annu Rev Immunol. 2002;20:29-53
11861596
Blood. 2002 Mar 1;99(5):1544-51
11861266
J Immunol. 2003 Mar 1;170(5):2765-75
12594308
Immunity. 2003 Feb;18(2):279-88
12594954
Nat Immunol. 2003 Mar;4(3):261-8
12577056
Annu Rev Immunol. 2003;21:231-64
12427767
J Exp Med. 2003 Apr 7;197(7):939-45
12682112
Immunity. 2003 Jun;18(6):801-11
12818161
Nat Immunol. 2003 Aug;4(8):765-72
12833154
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14163-8
14615582
Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3903-8
14988498
Clin Exp Med. 2004 Apr;3(4):211-7
15103511
J Immunol. 2004 Aug 15;173(4):2245-52
15294936
J Immunol. 2004 Aug 15;173(4):2331-41
15294946
Clin Exp Immunol. 2004 Sep;137(3):584-8
15320910
Nat Rev Immunol. 2004 Oct;4(10):775-86
15459669
Cancer Cell. 2004 Oct;6(4):399-408
15488762
Clin Immunol. 2004 Dec;113(3):234-40
15507387
Eur J Immunol. 1991 May;21(5):1123-30
2037009
Science. 1992 Apr 3;256(5053):105-7
1373518
J Clin Invest. 1992 Jun;89(6):1914-22
1351062
Science. 1995 Jun 2;268(5215):1347-9
7539157
Nature. 1995 Jul 27;376(6538):352-5
7543183
Adv Immunol. 1997;65:245-76
9238511
Science. 1997 Oct 3;278(5335):138-41
9311921
Mol Med. 1998 Feb;4(2):72-86
9508785
Nature. 1999 Jan 21;397(6716):263-6
9930702
Clin Immunol. 1999 Jul;92(1):34-48
10413651
J Biol Chem. 2005 Feb 25;280(8):7218-27
15542592
Curr Opin Immunol. 2005 Jun;17(3):282-9
15886118
Immunity. 2005 Jun;22(6):749-61
15963789
Scand J Immunol. 2005 Jun;61(6):566-74
15963052
Nat Genet. 2005 Aug;37(8):820-8
16007087
J Clin Immunol. 2005 Sep;25(5):496-502
16160919
Hum Genet. 2006 Feb;118(6):725-9
16328471
Blood. 2006 Apr 15;107(8):3045-52
16384931
N Engl J Med. 2006 May 4;354(18):1901-12
16672701
Eur J Hum Genet. 2006 Jul;14(7):867-75
16639407
Eur J Immunol. 2006 Jul;36(7):1892-903
16791882
J Immunol. 2006 Oct 1;177(7):4927-32
16982935
Nat Genet. 2007 Apr;39(4):429-30
17392797
Blood. 2007 Apr 1;109(7):2961-7
17119122
J Clin Invest. 2007 Jun;117(6):1550-7
17492055
J Immunol. 2000 Apr 15;164(8):4408-16
10754342