Inherited human ezrin deficiency impairs adaptive immunity
García-Solís, Blanca (Hospital Universitario La Paz (Madrid))
Van Den Rym, Ana (Hospital Universitario La Paz (Madrid))
Martinez-Martinez, Laura (Institut d'Investigació Biomèdica Sant Pau)
Franco-Leyva, Teresa (Institut d'Investigació Biomèdica Sant Pau)
Pérez-Caraballo, Jareb J. (Vanderbilt University Medical Center)
Markle, Janet (Vanderbilt University Medical Center)
Cubillos-Zapata, Carolina (Centre for Biomedical Research Network)
Marín, Ana V. (Centro de investigación Hospital Universitario 12 de Octubre)
Recio, María J. (Centro de investigación Hospital Universitario 12 de Octubre)
Regueiro, José R. (Centro de investigación Hospital Universitario 12 de Octubre)
Navarro-Zapata, Alfonso (Hospital Universitario La Paz (Madrid))
Mestre-Durín, Carmen (Hospital Universitario La Paz (Madrid))
Ferreras, Cristina (Hospital Universitario La Paz (Madrid))
Cotázar, Carla Martín (Hospital Universitario La Paz (Madrid))
Mena, Roció (Hospital Universitario La Paz (Madrid))
de la Calle-Fabregat, Carlos (Institut d'Investigació contra la Leucèmia Josep Carreras)
López-Lera, Alberto (Hospital Universitario La Paz (Madrid))
Arquero, Miguel Fernández (Hospital Clínico San Carlos (Madrid))
Pérez-Martínez, Antonio (Hospital Universitario La Paz (Madrid))
López-Collazo, Eduardo (Hospital Universitario La Paz (Madrid))
Sánchez-Ramón, Silvia (Hospital Clínico San Carlos (Madrid))
Casanova, Jean-Laurent (Howard Hughes Medical Institute)
Martínez-Barricarte, Rubén (Vanderbilt University Medical Center)
de la Calle-Martín, Oscar (Institut d'Investigació Biomèdica Sant Pau)
de Diego, Rebeca Pérez (Hospital Universitario La Paz (Madrid))
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	Inborn 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. Objective: We investigated a patient with an IEI of unknown genetic etiology. Whole-exome sequencing identified a homozygous missense mutation of the gene encoding ezrin (EZR), substituting a threonine for an alanine at position 129. Ezrin 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 central naive CD4 + cells. Autosomal-recessive human ezrin deficiency is a newly recognized genetic cause of B-cell deficiency affecting cellular and humoral immunity.
Grants:	Agencia Estatal de Investigación RTI2018-095673-B-I00 Instituto de Salud Carlos III PI22/00790 Instituto de Salud Carlos III PI17/00543
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Antibody deficiency ; Computational immunology ; EZR ; Inborn errors of immunity ; Lymphoid cells ; Mass cytometry ; Next-generation sequencing ; Primary immunodeficiency
Published in:	The Journal of Allergy and Clinical Immunology, Vol. 152 (june 2023) , p. 997-1009.e11, ISSN 1097-6825

DOI: 10.1016/j.jaci.2023.05.022
PMID: 37301410

26 p, 2.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles