Journal of Clinical Immunology

, Volume 32, Issue 1, pp 98–105 | Cite as

Parental Consanguinity is Associated with a Severe Phenotype in Common Variable Immunodeficiency

  • Claire Rivoisy
  • Laurence Gérard
  • David Boutboul
  • Marion Malphettes
  • Claire Fieschi
  • Isabelle Durieu
  • François Tron
  • Agathe Masseau
  • Pierre Bordigoni
  • Laurent Alric
  • Julien Haroche
  • Cyrille Hoarau
  • Alice Bérézné
  • Maryvonnick Carmagnat
  • Gael Mouillot
  • Eric Oksenhendler
  • for the DEFI study group


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.


CVID 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


B-cell linker


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.

Supplementary material

10875_2011_9604_MOESM1_ESM.pptx (208 kb)
ESM 1 (PPTX 207 kb)
10875_2011_9604_MOESM2_ESM.pptx (518 kb)
ESM 2 (PPTX 518 kb)


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Claire Rivoisy
    • 1
  • Laurence Gérard
    • 1
  • David Boutboul
    • 1
  • Marion Malphettes
    • 1
  • Claire Fieschi
    • 1
  • Isabelle Durieu
    • 2
  • François Tron
    • 3
  • Agathe Masseau
    • 4
  • Pierre Bordigoni
    • 5
  • Laurent Alric
    • 6
  • Julien Haroche
    • 7
  • Cyrille Hoarau
    • 8
  • Alice Bérézné
    • 9
  • Maryvonnick Carmagnat
    • 10
  • Gael Mouillot
    • 11
  • Eric Oksenhendler
    • 1
    • 12
  • for the DEFI study group
  1. 1.Department of Clinical Immunology, Hôpital Saint-LouisAssistance Publique-Hôpitaux de Paris and Université Paris DiderotParisFrance
  2. 2.Department of Internal MedicineCentre Hospitalier Lyon-SudPierre-BéniteFrance
  3. 3.Department of ImmunologyCHU de Rouen-Faculté de Médecine et PharmacieRouenFrance
  4. 4.Department of Internal MedicineCHU Hotel DieuNantesFrance
  5. 5.Pediatric OncologyHôpital BraboisVandoeuvre-les-NancyFrance
  6. 6.Department of Internal MedicineCHU Purpan, Paul Sabatier University Toulouse IIIToulouseFrance
  7. 7.Department of Internal Medicine, Hôpital de la SalpêtrièreAssistance Publique-Hôpitaux de ParisParisFrance
  8. 8.Department of Clinical Immunology and AllergyCHRU de ToursToursFrance
  9. 9.Department of Internal Medicine, Hôpital CochinAssistance Publique-Hôpitaux de ParisParisFrance
  10. 10.Immunology and Histocompatibility Laboratory, Hôpital Saint-LouisAssistance Publique-Hôpitaux de ParisParisFrance
  11. 11.Immunology Laboratory, INSERM UMR-S945, CIB Pitié-SalpêtrièreAssistance Publique-Hôpitaux de ParisParisFrance
  12. 12.Département d’Immunologie CliniqueHôpital Saint-LouisParisFrance

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