2. Academic Validation
  3. Lost in Translation: Lack of CD4 Expression due to a Novel Genetic Defect

Lost in Translation: Lack of CD4 Expression due to a Novel Genetic Defect

  • J Infect Dis. 2021 Feb 24;223(4):645-654. doi: 10.1093/infdis/jiab025.
Andrea Lisco 1,  Peying Ye 1,  Chun-Shu Wong 1,  Luxin Pei 1,  Amy P Hsu 1,  Emily M Mace 2,  Jordan S Orange 2,  Silvia Lucena Lage 1,  Addison Jon Ward 1,  Stephen A Migueles 1,  Mark Connors 1,  Megan V Anderson 1,  Clarisa M Buckner 1,  Susan Moir 1,  Adam Rupert 3,  Alina Dulau-Florea 4,  Princess Ogbogu 5,  Dylan Timberlake 5,  Luigi D Notarangelo 1,  Stefania Pittaluga 6,  Roshini S Abraham 7,  Irini Sereti 1
Affiliations

Affiliations

  • 1 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • 2 Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA.
  • 3 Leidos Biomedical Research, Inc, Frederick, Maryland, USA.
  • 4 National Institutes of Health Clinical Center, Bethesda, Maryland, USA.
  • 5 Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
  • 6 National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • 7 Nationwide Children`s Hospital, Columbus, Ohio, USA.
PMID: 33471124 DOI: 10.1093/infdis/jiab025
Abstract

CD4 expression identifies a subset of mature T cells primarily assisting the germinal center reaction and contributing to CD8+ T-cell and B-cell activation, functions, and longevity. Herein, we present a family in which a novel variant disrupting the translation-initiation codon of the CD4 gene resulted in complete loss of membrane and plasma soluble CD4 in peripheral blood, lymph node, bone marrow, skin, and ileum of a homozygous proband. This inherited CD4 knockout disease illustrates the clinical and immunological features of a complete deficiency of any functional component of CD4 and its similarities and differences with other clinical models of primary or acquired loss of CD4+ T cells. The first inherited loss of any functional component of CD4, including soluble CD4, is clinically distinct from any other congenital or acquired CD4 T-cell defect and characterized by compensatory changes in T-cell subsets and functional impairment of B cells, monocytes, and natural killer cells.

Keywords

CD4 deficiency; double-negative T cells; immunizations; recurrent pneumonia.

Figures