Parental consanguinity is associated with a severe phenotype in common variable immunodeficiency.

Area of Science:

• Immunology
• Genetics
• Clinical Medicine

Background:

• Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by low immunoglobulin levels and impaired B-cell function.
• Parental consanguinity, a state where parents are related, can increase the risk of autosomal recessive genetic disorders.

Purpose of the Study:

• To investigate the clinical and immunological differences between CVID patients with and without parental consanguinity.
• To determine if parental consanguinity is associated with increased disease severity or specific complications in CVID.

Main Methods:

• The DEFI study collected clinical data and biological specimens from CVID patients.
• Patients were categorized into two groups: those with consanguineous parents (cCVID) and those without (ncCVID).
• Clinical outcomes, B-cell subsets, and T-cell populations were compared between the two groups.

Main Results:

• Consanguineous CVID patients experienced higher rates of splenomegaly, granulomatous disease, bronchiectasis, and opportunistic infections compared to non-consanguineous patients.
• While B-cell subsets were similar, cCVID patients showed decreased naïve CD4+ T cells and increased activated CD4+ and CD8+ T cells.
• Age at symptom onset and diagnosis were comparable between groups.

Conclusions:

• Parental consanguinity is associated with an increased risk of severe clinical complications in CVID patients.
• These patients often present with significant T-cell abnormalities, suggesting a potential diagnosis of late-onset combined immune deficiency (LOCID).
• Investigating parental consanguinity in CVID aids in tailored clinical care and genetic screening.