title: Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect.
abstract: BACKGROUND
  Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs).
  
  
  METHODS
  The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs.
  
  
  RESULTS
  Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4(+) T cell count <200 x 10(6) cells/L, and were compared with the remaining 285 patients with CVID. The patients with LOCID more frequently belonged to consanguineous families (29% vs 8%; P = .004). They differed from patients with CVID with a higher prevalence of splenomegaly (64% vs 31%), granuloma (43% vs 10%), gastrointestinal disease (75% vs 42%), and lymphoma (29% vs 4%). Even on immunoglobulin substitution, they required more frequent antibiotics administration and hospitalization. Lymphocyte counts were lower, with a marked decrease in CD4(+) T cell counts (158 x 10(6) vs 604 x 10(6) cells/L; P < .001) and a severe defect in naive CD45RA(+)CCR7(+)CD4(+) T cell counts (<20% of total CD4(+) T cells in 71% of patients with LOCID vs 37% of patients with CVID; P = .001). The CD19(+) B cell compartment was also significantly decreased (20 x 10(6) vs 102 x 10(6) cells/L; P < .001).
  
  
  CONCLUSIONS
  LOCID differs from classic CVID in its clinical and immunologic characteristics. Systematic T cell phenotype may help to discriminate such patients from those with CVID. Identification of this phenotype should result in a more fitted diagnostic and therapeutic approach of infections and could provide insights for genetic diagnosis.
authors.affiliation: Département d'Immunologie, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France. marion.malphettes@sls.aphp.fr
authors.forename: Marion
authors.initials: M
authors.lastname: Malphettes
authors.forename: Laurence
authors.initials: L
authors.lastname: Gérard
authors.forename: Maryvonnick
authors.initials: M
authors.lastname: Carmagnat
authors.forename: Gaël
authors.initials: G
authors.lastname: Mouillot
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vince
authors.forename: David
authors.initials: D
authors.lastname: Boutboul
authors.forename: Alice
authors.initials: A
authors.lastname: Bérezné
authors.forename: Raphaële
authors.initials: R
authors.lastname: Nove-Josserand
authors.forename: Vincent
authors.initials: V
authors.lastname: Lemoing
authors.forename: Laurent
authors.initials: L
authors.lastname: Tetu
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Viallard
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
authors.forename: Michel
authors.initials: M
authors.lastname: Pavic
authors.forename: Julien
authors.initials: J
authors.lastname: Haroche
authors.forename: Claire
authors.initials: C
authors.lastname: Larroche
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Brouet
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fermand
authors.forename: Claire
authors.initials: C
authors.lastname: Rabian
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology / Q000473:pathology; D017668:Age of Onset; D000368:Aged; D017074:Common Variable Immunodeficiency / Q000150:complications* / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000209:etiology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D055815:Young Adult