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

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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.

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Abbreviations

CVID:

Common variable immunodeficiency

cCVID:

Common variable immunodeficiency in patients with consanguineous parents

ncCVID:

Common variable immunodeficiency in patients with non-consanguineous parents

LOCID:

Late-onset combined immune deficiency

ICOS:

Inducible T-cell costimulator

BAFF-R:

B cell-activating factor receptor

TACI:

Transmembrane activator and CAML interactor

BLNK:

B-cell linker

EBV:

Epstein Barr virus

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Acknowledgments

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.

Author information

Authors and Affiliations

  1. Department of Clinical Immunology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris and Université Paris Diderot, Sorbonne Paris Cité, EA3963, Paris, France

    Claire Rivoisy, Laurence Gérard, David Boutboul, Marion Malphettes, Claire Fieschi & Eric Oksenhendler

  2. Department of Internal Medicine, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France

    Isabelle Durieu

  3. Department of Immunology, CHU de Rouen-Faculté de Médecine et Pharmacie, Rouen, France

    François Tron

  4. Department of Internal Medicine, CHU Hotel Dieu, Nantes, France

    Agathe Masseau

  5. Pediatric Oncology, Hôpital Brabois, Vandoeuvre-les-Nancy, France

    Pierre Bordigoni

  6. Department of Internal Medicine, CHU Purpan, Paul Sabatier University Toulouse III, Toulouse, France

    Laurent Alric

  7. Department of Internal Medicine, Hôpital de la Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France

    Julien Haroche

  8. Department of Clinical Immunology and Allergy, CHRU de Tours, Tours, France

    Cyrille Hoarau

  9. Department of Internal Medicine, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France

    Alice Bérézné

  10. Immunology and Histocompatibility Laboratory, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France

    Maryvonnick Carmagnat

  11. Immunology Laboratory, INSERM UMR-S945, CIB Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France

    Gael Mouillot

  12. Département d’Immunologie Clinique, Hôpital Saint-Louis, 1 avenue Claude Vellefaux, 75010, Paris, France

    Eric Oksenhendler

Authors
  1. Claire Rivoisy
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  2. Laurence Gérard
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  3. David Boutboul
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  4. Marion Malphettes
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  5. Claire Fieschi
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  6. Isabelle Durieu
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  7. François Tron
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  8. Agathe Masseau
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  9. Pierre Bordigoni
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  10. Laurent Alric
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  11. Julien Haroche
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  12. Cyrille Hoarau
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  13. Alice Bérézné
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  14. Maryvonnick Carmagnat
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  15. Gael Mouillot
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  16. Eric Oksenhendler
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Consortia

for the DEFI study group

Corresponding author

Correspondence to Eric Oksenhendler.

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Appendix

Appendix

DEFI study group

  • Coordination: E. Oksenhendler, Hôpital Saint Louis, Paris

  • Clinical Centers: Hôpital Saint Louis, Paris: C. Fieschi, M. Malphettes, L. Galicier, D. Boutboul, J.P. Fermand. Bordeaux: J.F. Viallard. Limoges: A. Jaccard. Tours: C. Hoarau, Y. Lebranchu. Hôpital Cochin, Paris: A. Bérezné, L. Mouthon. HEGP, Paris: M. Karmochkine, S. Georgin-Lavialle. Marseille: N. Schleinitz. Lyon Sud: I. Durieu, R. Nove-Josserand. Clermont-Ferrand: V. Chanet. Montpellier: V. Le-Moing. Roubaix: N. Just. Hôtel-Dieu, Paris: C. Salanoubat. Reims: R. Jaussaud. Hôpital Necker, Paris: F. Suarez, O. Hermine. Le Mans: P. Solal-Celigny. Lille: E. Hachulla. Perpignan: L. Sanhes. Angers: M. Gardembas, I. Pellier. Troyes: P. Tisserant. Lyon Armée: M. Pavic. Dijon: B. Bonnotte. Pitié-Salpêtrière, Paris: J. Haroche, Z. Amoura. Toulouse: L. Alric, M.F. Thiercelin, L. Tetu, D. Adoue. Nancy Vandoeuvre: P. Bordigoni. Lyon Croix Rousse: T. Perpoint. Lyon Hotel-Dieu: P. Sève. Besançon: P. Rohrlich. Strasbourg: J.L. Pasquali, P. Soulas. Hôpital Foch, Suresnes: L.J. Couderc, E. Catherinot. Montauban: P. Giraud. Hôpital Saint-Louis, Pédiatrie, Paris: A. Baruchel. Clermont-Ferrand 2: I. Deleveau. Kremlin-Bicêtre: F. Chaix. Hôpital Trousseau, Paris: J. Donadieu. Rouen: F. Tron. Bobigny: C. Larroche. Aix: AP Blanc. Nantes: A. Masseau, M. Hamidou. Nancy: G. Kanny, M. Morisset. Poitiers: F. Millot. Bondy: O. Fain. Hôpital Bichat, Paris: R. Borie. Rennes: A. Perlat. Clamart: V. Martinez. Caen: B. Bienvenu.

  • Labs

    Pitié-Salpêtrière, INSERM U543, Paris: P. Debré, G. Mouillot, I. Théodorou.

    Saint-Louis, Immunologie, Paris: C. Rabian, M. Carmagnat.

    Saint-Louis, EA 3963, Paris: C. Fieschi, M. Malphettes, N. Vince, D. Boutboul

  • Data Management and Statistics: L. Gérard.

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Rivoisy, C., Gérard, L., Boutboul, D. et al. Parental Consanguinity is Associated with a Severe Phenotype in Common Variable Immunodeficiency. J Clin Immunol 32, 98–105 (2012). https://doi.org/10.1007/s10875-011-9604-9

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  • DOI: https://doi.org/10.1007/s10875-011-9604-9

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