The following is a summary of “Rapidly Expanding Genetic Spectrum of Common Variable Immunodeficiency–Like Disorders,” published in the June 2023 issue of Allergy and Clinical Immunology by Ameratunga, et al.

Common variable immunodeficiency disorders (CVID) are still poorly understood. CVID was previously an exclusionary diagnosis. New diagnostic criteria have enabled a more precise identification of the disease. With the advent of next-generation sequencing (NGS), it has become evident that many patients with a CVID phenotype possess a causative genetic variant. If a pathogenic variant is identified, these patients are reclassified as having a CVID-like disorder rather than CVID. 

In populations where consanguinity is more common, most patients with severe primary hypogammaglobulinemia will have an underlying inborn immunity error, typically an autosomal recessive disorder with an early onset. Pathogenic variants are identified in approximately 20% to 30% of patients in nonconsanguineous societies. These mutations are frequently autosomal dominant with variable penetrance and expressivity. Some genetic variants, such as those in TNFSF13B (transmembrane activator calcium modulator cyclophilin ligand interactor), predispose or exacerbate disease severity, adding to the complexity of CVID and CVID-like disorders. 

These variants are not causal, but they may interact epistatically (synergetically) with more deleterious mutations to exacerbate disease severity. The current understanding of the genes associated with CVID and CVID-like disorders is described in this article. When investigating the genetic basis of disease in patients with a CVID phenotype, this information will aid clinicians in interpreting NGS reports.

Source: sciencedirect.com/science/article/abs/pii/S2213219823001745