title: Low Circulating Natural Killer Cell Counts are Associated With Severe Disease in Patients With Common Variable Immunodeficiency.
abstract: Natural Killer (NK) cells have been shown to exert antiviral and antitumoural activities. Nevertheless most available data are derived from mouse models and functions of these cells in human remain unclear. To evaluate the impact of low circulating NK cell counts and to provide some clues to the role of NK cells in natural conditions, we studied a large cohort of patients with common variable immunodeficiency (CVID) included in a multicenter cohort of patients with primary hypogammaglobulinaemia. Patients were classified into three groups on the basis of their NK cell counts: severe and mild NK cell lymphopenia (<50 and 50-99×10(6)/L respectively), and normal NK cell counts (>100×10(6)/L). Clinical events were analyzed and compared between these three groups of patients. During study period, 457 CVID patients were included: 99 (21.7%) with severe NK cell lymphopenia, 118 (25.8%) with mild NK cell lymphopenia and 240 (52.5%) with normal NK cell counts. Non-infectious complications (57% vs. 36% and 35%), and, particularly, granulomatous complications (25.3% vs. 13.6% and 8.8%), were more frequent in patients with severe NK cell lymphopenia than in other groups. Invasive infections (68.7% vs. 60.2% and 48.8%), including bacteraemia (22.2% vs. 5.9% and 8.3%) and infectious pneumonia (63.6% vs. 59.3% and 44.2%), were also more frequent in this population. However, no difference was observed for viral infections and neoplasms. Low circulating NK cell counts are associated with more severe phenotypes of CVID, which may indicate a protective role of these immune cells against severe bacterial infections and other complications and non-redundant immune functions when the adaptive immune response is not optimal.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University UM2, 13288 Marseille, France; Inserm U1104, 13288 Marseille, France; CNRS UMR7280, 13288 Marseille, France; Médecine Interne, Hôpital de la Timone, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille University, 13005 Marseille, France.
authors.forename: Mikael
authors.initials: M
authors.lastname: Ebbo
authors.affiliation: Immunopathologie Clinique, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris, 75010 Paris, France; EA3518, University Paris 7 Denis Diderot, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Gérard
authors.affiliation: MI-mAbs Consortium (Aix Marseille University), CIML, 13288 Marseille, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Carpentier
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University UM2, 13288 Marseille, France; Inserm U1104, 13288 Marseille, France; CNRS UMR7280, 13288 Marseille, France; Immunologie, Hôpital de la Conception, Assistance Publique -Hôpitaux de Marseille, 13385 Marseille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Vély
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University UM2, 13288 Marseille, France; Inserm U1104, 13288 Marseille, France; CNRS UMR7280, 13288 Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Cypowyj
authors.affiliation: Immunologie, Hôpital de la Conception, Assistance Publique -Hôpitaux de Marseille, 13385 Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Farnarier
authors.affiliation: Inserm U1126, University Paris 7 Denis Diderot, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vince
authors.affiliation: Immunopathologie Clinique, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris, 75010 Paris, France; Inserm U1126, University Paris 7 Denis Diderot, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Malphettes
authors.affiliation: Immunopathologie Clinique, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris, 75010 Paris, France; Inserm U1126, University Paris 7 Denis Diderot, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.affiliation: Immunopathologie Clinique, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris, 75010 Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University UM2, 13288 Marseille, France; Inserm U1104, 13288 Marseille, France; CNRS UMR7280, 13288 Marseille, France; Médecine Interne, Hôpital de la Timone, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille University, 13005 Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schleinitz
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille University UM2, 13288 Marseille, France; Inserm U1104, 13288 Marseille, France; CNRS UMR7280, 13288 Marseille, France; MI-mAbs Consortium (Aix Marseille University), CIML, 13288 Marseille, France. Electronic address: vivier@ciml.univ-mrs.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
mesh_terms: D000328:Adult; D015331:Cohort Studies; D017074:Common Variable Immunodeficiency / Q000145:classification* / Q000150:complications / Q000276:immunology*; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology*; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000150:complications / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged
keywords: Common variable immunodeficiency (CVID); Granuloma; Innate immunity; Invasive bacterial infections; Natural Killer cells (NK cells); Redundancy of immune system