CD27 deficiency is associated with combined immunodeficiency and persistent symptomatic EBV viremia

J Allergy Clin Immunol. 2012 Mar;129(3):787-793.e6. doi: 10.1016/j.jaci.2011.11.013. Epub 2011 Dec 24.

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.

Conclusion: 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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Agammaglobulinemia / etiology
  • Anemia, Aplastic / complications
  • Anemia, Aplastic / genetics
  • Anemia, Aplastic / immunology*
  • Anemia, Aplastic / physiopathology
  • Anemia, Aplastic / virology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Cells, Cultured
  • Consanguinity
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / genetics
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / physiopathology
  • Epstein-Barr Virus Infections / virology
  • Fatal Outcome
  • Gram-Positive Bacterial Infections / complications
  • Gram-Positive Bacterial Infections / genetics
  • Gram-Positive Bacterial Infections / immunology*
  • Gram-Positive Bacterial Infections / physiopathology
  • Gram-Positive Bacterial Infections / virology
  • Herpesvirus 4, Human / immunology*
  • Herpesvirus 4, Human / pathogenicity
  • Humans
  • Immunity, Humoral / genetics
  • Male
  • Mutation / genetics
  • Pedigree
  • Severe Combined Immunodeficiency / complications
  • Severe Combined Immunodeficiency / genetics
  • Severe Combined Immunodeficiency / immunology*
  • Severe Combined Immunodeficiency / physiopathology
  • Severe Combined Immunodeficiency / virology
  • Siblings
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics*
  • Viremia / genetics
  • Viremia / immunology*
  • Viremia / virology
  • Young Adult

Substances

  • Tumor Necrosis Factor Receptor Superfamily, Member 7