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
  • 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.