Parental Consanguinity is Associated with a Severe Phenotype in Common Variable Immunodeficiency
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The DEFI study has collected clinical data and biological specimens from kindreds with CVID. Patients with demonstrated parental consanguinity (cCVID group) were compared to patients without parental consanguinity (ncCVID). A total of 24 of the 436 patients with CVID had consanguineous parents. Age at first symptoms and age at diagnosis were comparable in the two groups. Some complications were more frequent in cCVID patients: splenomegaly (62.5% vs. 29%; p = 0.001), granulomatous disease (29% vs. 12%; p = 0.02), and bronchiectasis (58% vs. 29%; p = 0.003). A high incidence of opportunistic infections was also observed in this population (29% vs. 5%; p < 0.001). Distribution of B-cell subsets were similar in the two groups. Naïve CD4+ T cells were decreased in cCVID patients (15% vs. 28%; p < 0.001), while activated CD4 + CD95+ (88% vs. 74%; p = 0.002) and CD8 + HLA-DR + T cells (47% vs. 31%; p < 0.001) were increased in these patients when compared to ncCVID patients. Parental consanguinity is associated with an increased risk of developing severe clinical complications in patients with CVID. Most of these patients presented with severe T-cell abnormalities and should be considered with a diagnosis of late-onset combined immune deficiency (LOCID). Systematic investigation for parental consanguinity in patients with CVID provides useful information for specific clinical care and genetic screening.
KeywordsCVID consanguinity antibody deficiency primary immune deficiency
Common variable immunodeficiency
Common variable immunodeficiency in patients with consanguineous parents
Common variable immunodeficiency in patients with non-consanguineous parents
Late-onset combined immune deficiency
Inducible T-cell costimulator
B cell-activating factor receptor
Transmembrane activator and CAML interactor
Epstein Barr virus
The DEFI study was supported by a national program for clinical research (PHRC 2005) and by the National Center on Hereditary Immune Deficiencies (CEREDIH), by Laboratoire Français du Fractionnement et des Biotechnologies (LFB), Baxter BioScience, and CSL Behring.
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