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

Delfien J A Bogaert; Melissa Dullaers; Bart N Lambrecht; Karim Y Vermaelen; Elfride De Baere; Filomeen Haerynck

doi:10.1136/jmedgenet-2015-103690

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.

Authors

Delfien J A Bogaert¹, Melissa Dullaers², Bart N Lambrecht³, Karim Y Vermaelen⁴, Elfride De Baere⁵, Filomeen Haerynck⁶

Affiliations

¹ Clinical Immunology Research Lab, Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium Department of Pediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium.
² Clinical Immunology Research Lab, Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium Department of Internal Medicine, Ghent University, Ghent, Belgium.
³ Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium Department of Internal Medicine, Ghent University, Ghent, Belgium.
⁴ Clinical Immunology Research Lab, Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium Department of Internal Medicine, Ghent University, Ghent, Belgium Tumor Immunology Laboratory, Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium.
⁵ Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
⁶ Clinical Immunology Research Lab, Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Belgium Department of Pediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium.

PMID: 27250108
DOI: 10.1136/jmedgenet-2015-103690

Abstract

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.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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