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

Area of Science:

• Immunology
• Genetics

Background:

• Common variable immunodeficiency (CVID) is a primary antibody deficiency characterized by hypogammaglobulinaemia and increased susceptibility to infections.
• CVID exhibits significant phenotypical and genetic heterogeneity, with monogenic forms accounting for only 2-10% of cases.

Purpose of the Study:

• To review the current understanding of the molecular genetic basis of CVID.
• To emphasize the relationship between genetic defects and the clinical and immunological phenotype in CVID patients.

Main Methods:

• Literature review of genetic studies in CVID.
• Analysis of identified genes and their association with clinical manifestations.

Main Results:

• Numerous genes have been implicated in monogenic CVID, including ICOS, TNFRSF13B, IL21, and LRBA.
• CVID is increasingly recognized as an umbrella diagnosis, with genetic defects defining distinct disease entities.
• Evidence suggests complex or polygenic inheritance in a subgroup of CVID patients.

Conclusions:

• The genetic landscape of CVID is complex, encompassing both monogenic and potentially polygenic forms.
• Understanding the molecular genetic basis is crucial for classifying CVID subtypes and correlating them with clinical and immunological phenotypes.