Lost in Translation: Lack of CD4 Expression due to a Novel Genetic Defect. (20th January 2021)

• Record Type: Journal Article
• Authors: Lisco, Andrea; Ye, Peiying; Wong, Chun-Shu; Pei, Luxin; Hsu, Amy P; Mace, Emily M; Orange, Jordan S; Lage, Silvia Lucena; Ward, Addison Jon; Migueles, Stephen A; Connors, Mark; Anderson, Megan V; Buckner, Clarisa M; Moir, Susan; Rupert, Adam; Dulau-Florea, Alina; Ogbogu, Princess; Timberlake, Dylan; Notarangelo, Luigi D; Pittaluga, Stefania; Abraham, Roshini S; Sereti, Irini
• Is Part Of: Journal of infectious diseases. Volume 223:Number 4(2021)
• Page Start: 645
• Page End: 654
• Publication Date: 2021-01-20
• Subjects: CD4 deficiency -- recurrent pneumonia -- immunizations -- double-negative T cells; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiab025
• Languages: English
• ISSNs: 0022-1899

Abstract

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. Abstract : 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, monocyte and NK-cells.