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

• Published in: Journal of allergy and clinical immunology Vol. 129; no. 3; pp. 787 - 793.e6
• Main Authors: van Montfrans, Joris M., MD, PhD, Hoepelman, Andy I.M., MD, PhD, Otto, Sigrid, BSc, van Gijn, Marielle, PhD, van de Corput, Lisette, PhD, de Weger, Roel A., PhD, Monaco-Shawver, Linda, BSc, Banerjee, Pinaki P., PhD, Sanders, Elisabeth A.M., MD, PhD, Jol–van der Zijde, Cornelia M., PhD, Betts, Michael R., PhD, Orange, Jordan S., MD, PhD, Bloem, Andries C., PhD, Tesselaar, Kiki, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.03.2012; Elsevier; Elsevier Limited
• Subjects: Agammaglobulinemia - etiology; Age; Allergy and Immunology; Anemia, Aplastic - complications; Anemia, Aplastic - genetics; Anemia, Aplastic - immunology; Anemia, Aplastic - physiopathology; Anemia, Aplastic - virology; Aplastic anemia; B cell; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Biological and medical sciences; CD27; CD27 antigen; Cell survival; Cells, Cultured; Consanguinity; Costimulator; Differentiation; EBV; Epstein-Barr virus; 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; Family medical history; Fatal Outcome; Fever; Fundamental and applied biological sciences. Psychology; Fundamental immunology; 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; Hypogammaglobulinemia; Immune system; Immunity, Humoral - genetics; Immunodeficiency; Immunoglobulins; Immunopathology; Infection; Infections; Infectious diseases; Ligands; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Medical sciences; Mutation; Mutation - genetics; natural killer cell; Natural killer cells; Patients; Pedigree; phenotype; Plasma cells; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sepsis; Severe Combined Immunodeficiency - complications; Severe Combined Immunodeficiency - genetics; Severe Combined Immunodeficiency - immunology; Severe Combined Immunodeficiency - physiopathology; Severe Combined Immunodeficiency - virology; Siblings; T cell; T cell receptors; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; Tumor Necrosis Factor Receptor Superfamily, Member 7 - genetics; Viral diseases; Viral infections; Viremia; Viremia - genetics; Viremia - immunology; Viremia - virology; Young Adult; TT; Common variable immunodeficiency; hypogammaglobulinemia; FACS; Pokeweed mitogen; B cell; CVID; Germinal center; EBV; immunodeficiency; natural killer cell; GC; viremia; Cytotoxic T lymphocyte; phenotype; Staphylococcus aureus Cowan I antigen; T cell; PWM; Fluorescence-activated cell sorting; SAC; Natural killer; Tetanus toxoid; CD27; CTL; NK; Gammaherpesvirinae; Immunopathology; Viremia; Herpesviridae; Deficiency; Agammaglobulinemia; B-Lymphocyte; Epstein Barr virus; Infection; Virus; Natural killer cell; Phenotype; Association; Immunology; Viral disease; T-Lymphocyte; Combined immune deficiency
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2011.11.013

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.