title: Parental consanguinity is associated with a severe phenotype in common variable immunodeficiency.
abstract: 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.
authors: Department of Clinical Immunology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Sorbonne Paris Cité, EA3963, Paris, France.
authors: Claire
authors: C
authors: Rivoisy
authors: Laurence
authors: L
authors: Gérard
authors: David
authors: D
authors: Boutboul
authors: Marion
authors: M
authors: Malphettes
authors: Claire
authors: C
authors: Fieschi
authors: Isabelle
authors: I
authors: Durieu
authors: François
authors: F
authors: Tron
authors: Agathe
authors: A
authors: Masseau
authors: Pierre
authors: P
authors: Bordigoni
authors: Laurent
authors: L
authors: Alric
authors: Julien
authors: J
authors: Haroche
authors: Cyrille
authors: C
authors: Hoarau
authors: Alice
authors: A
authors: Bérézné
authors: Maryvonnick
authors: M
authors: Carmagnat
authors: Gael
authors: G
authors: Mouillot
authors: Eric
authors: E
authors: Oksenhendler
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D017074:Common Variable Immunodeficiency / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology; D003241:Consanguinity; D005260:Female; D005602:France; D056726:Genetic Association Studies; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D055815:Young Adult