title: CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia.
abstract: BACKGROUND
  CD27 is a lymphocyte costimulatory molecule that regulates T-cell, natural killer (NK) cell, B-cell, and plasma cell function, survival, and differentiation. On the basis of its function and expression pattern, we considered CD27 a candidate gene in patients with hypogammaglobulinemia.
  
  
  OBJECTIVE
  We sought to describe the clinical and immunologic phenotypes of patients with genetic CD27 deficiency.
  
  
  METHODS
  A molecular and extended immunologic analysis was performed on 2 patients lacking CD27 expression.
  
  
  RESULTS
  We identified 2 brothers with a homozygous mutation in CD27 leading to absence of CD27 expression. Both patients had persistent symptomatic EBV viremia. The index patient was hypogammaglobulinemic, and immunoglobulin replacement therapy was initiated. His brother had aplastic anemia in the course of his EBV infection and died from fulminant gram-positive bacterial sepsis. Immunologically, lack of CD27 expression was associated with impaired T cell-dependent B-cell responses and T-cell dysfunction.
  
  
  CONCLUSIONS
  Our findings identify a role for CD27 in human subjects and suggest that this deficiency can explain particular cases of persistent symptomatic EBV viremia with hypogammaglobulinemia and impaired T cell-dependent antibody generation.
authors.affiliation: Departments of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Joris M
authors.initials: JM
authors.lastname: van Montfrans
authors.forename: Andy I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: Sigrid
authors.initials: S
authors.lastname: Otto
authors.forename: Marielle
authors.initials: M
authors.lastname: van Gijn
authors.forename: Lisette
authors.initials: L
authors.lastname: van de Corput
authors.forename: Roel A
authors.initials: RA
authors.lastname: de Weger
authors.forename: Linda
authors.initials: L
authors.lastname: Monaco-Shawver
authors.forename: Pinaki P
authors.initials: PP
authors.lastname: Banerjee
authors.forename: Elisabeth A M
authors.initials: EA
authors.lastname: Sanders
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Jol-van der Zijde
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Orange
authors.forename: Andries C
authors.initials: AC
authors.lastname: Bloem
authors.forename: Kiki
authors.initials: K
authors.lastname: Tesselaar
mesh_terms: D000361:Agammaglobulinemia / Q000209:etiology; D000741:Anemia, Aplastic / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003241:Consanguinity; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D017809:Fatal Outcome; D016908:Gram-Positive Bacterial Infections / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D035781:Siblings; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics*; D014766:Viremia / Q000235:genetics / Q000276:immunology* / Q000821:virology; D055815:Young Adult
chemical_list: D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7