RT Journal Article
T1 Inherited human ezrin deficiency impairs adaptive immunity
A1 García-Solís, Blanca et al.
A1 Rebeca Pérez de Diego, 
A1 Martínez Martínez, Laura María
A1 Recio Hoyas, María José
A1 Fernández Arquero, Miguel
A1 Sánchez Ramón, Silvia María
AB BackgroundInborn errors of immunity (IEI) are a group of monogenic diseases that confer susceptibility to infection, autoimmunity, and cancer. Despite the life-threatening consequences of some IEI, their genetic cause remains unknown in many patients.ObjectiveWe investigated a patient with an IEI of unknown genetic etiology.MethodsWhole-exome sequencing identified a homozygous missense mutation of the gene encoding ezrin (EZR), substituting a threonine for an alanine at position 129.ResultsEzrin is one of the subunits of the ezrin, radixin, and moesin (ERM) complex. The ERM complex links the plasma membrane to the cytoskeleton and is crucial for the assembly of an efficient immune response. The A129T mutation abolishes basal phosphorylation and decreases calcium signaling, leading to complete loss of function. Consistent with the pleiotropic function of ezrin in myriad immune cells, multidimensional immunophenotyping by mass and flow cytometry revealed that in addition to hypogammaglobulinemia, the patient had low frequencies of switched memory B cells, CD4+ and CD8+ T cells, MAIT, γδ T cells, and centralnaive CD4+ cells.ConclusionsAutosomal-recessive human ezrin deficiency is a newly recognized genetic cause of B-cell deficiency affecting cellular and humoral immunity.
PB Elsevier
SN 0091-6749
YR 2023
FD 2023-10
LK https://hdl.handle.net/20.500.14352/92656
UL https://hdl.handle.net/20.500.14352/92656
LA eng
NO García-Solís B, Van Den Rym A, Martinez-Martínez L, Franco T, Pérez-Caraballo JJ, Markle J, Cubillos-Zapata C, Marín AV, Recio MJ, Regueiro JR, Navarro-Zapata A, Mestre-Durán C, Ferreras C, Martín Cotázar C, Mena R, de la Calle-Fabregat C, López-Lera A, Fernández Arquero M, Pérez-Martínez A, López-Collazo E, Sánchez-Ramón S, Casanova JL, Martínez-Barricarte R, de la Calle-Martín O, Pérez de Diego R. J Allergy Clin Immunol. 2023 Oct;152(4):997-1009
NO ISCIII (Instituto de Salud Carlos III)
NO MINECO (Ministerio de Economía y competitividad)
NO National Institutes of Health (NIH)
NO National Institute of Allergy and Infectious Diseases of the NIH
NO National Center for Advancing Translational Sciences
DS Docta Complutense
RD 29 sept 2024