Genes associated with common variable immunodeficiency: one diagnosis to rule them all?

J Med Genet. 2016 Sep;53(9):575-90. doi: 10.1136/jmedgenet-2015-103690. Epub 2016 Jun 1.


Common variable immunodeficiency (CVID) is a primary antibody deficiency characterised by hypogammaglobulinaemia, impaired production of specific antibodies after immunisation and increased susceptibility to infections. CVID shows a considerable phenotypical and genetic heterogeneity. In contrast to many other primary immunodeficiencies, monogenic forms count for only 2-10% of patients with CVID. Genes that have been implicated in monogenic CVID include ICOS, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF12 (TWEAK), CD19, CD81, CR2 (CD21), MS4A1 (CD20), TNFRSF7 (CD27), IL21, IL21R, LRBA, CTLA4, PRKCD, PLCG2, NFKB1, NFKB2, PIK3CD, PIK3R1, VAV1, RAC2, BLK, IKZF1 (IKAROS) and IRF2BP2 With the increasing number of disease genes identified in CVID, it has become clear that CVID is an umbrella diagnosis and that many of these genetic defects cause distinct disease entities. Moreover, there is accumulating evidence that at least a subgroup of patients with CVID has a complex rather than a monogenic inheritance. This review aims to discuss current knowledge regarding the molecular genetic basis of CVID with an emphasis on the relationship with the clinical and immunological phenotype.

Keywords: Common Variable Immunodeficiency; Complex inheritance; Genetics; Hypogammaglobulinemia; Monogenic.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Common Variable Immunodeficiency / diagnosis*
  • Common Variable Immunodeficiency / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Molecular Biology / methods