Common variable immunodeficiency (CVID) [62 genes]

Common variable immunodeficiency (CVID) is adults’ most frequently diagnosed symptomatic primary immunodeficiency. CVID encompasses a heterogeneous set of diseases that share common characteristics. The pathophysiology of CVID is due to a defect in the cellular humoral response caused by a failure of B cell differentiation, an absence of immunoglobulin production, defective T cell signaling, or an interaction altered between B and T cells. Monogenic, oligogenic, and polygenic forms of CVID have been described, so the interpretation of the genetic study is complex in this type of pathology.

• 1/10,000 – 1/50,000 individuals

CVID comprises a heterogeneous group of diseases of the immune system in which monogenic forms with an autosomal dominant, autosomal recessive and X-linked inheritance pattern have been reported. Oligogenic causes have also been reported, in which more than one genetic defect has been identified in different genes that are part of the same biochemical pathway or, even, polygenic forms in which the genetic component can be made up of different risk factors or genetically based modulating factors.

The identification of a genetic cause provides critical information about the inheritance pattern and behavior of the disease, which may have different evolution depending on the gene that is mutated.

A genetic study for CVID is recommended in those patients who meet the diagnostic criteria. According to the ESID, the revised diagnostic criteria for CVID are:

1. At least one of the following with a decrease in IgG and a decrease in IgA with or without low levels of IgM (measured at least twice; <2 SD of normal levels for your age)
• Increased susceptibility to infections
• Autoimmune manifestations
• Granulomatous disease
• Idiopathic polyclonal lymphoproliferation
• Family history with antibody deficiency
2. Along with at least one of the following:
• Poor antibody response to vaccines
• Reduced levels of Switched Memory B Cells.
3. Secondary causes of hypogammaglobulinemia have been excluded.
4. The diagnosis is established after the fourth year of life (but symptoms may be present earlier).
5. There is no evidence of profound T cell deficiency, defined as two of the following.

Although the diagnostic performance data is variable and sometimes depends on the number of genes included in the diagnostic panel, it does not exceed 35% of cases diagnosed with CVID in which a genetic cause is identified according to the scientific literature.