AI Article Synopsis
- Inborn errors of immunity (IEI) are genetic disorders that make individuals more vulnerable to infections, autoimmune diseases, and cancer, but many cases lack a known genetic cause.
- Researchers studied a patient with an IEI and found a specific mutation in the ezrin (EZR) gene that negatively affected immune function.
- The study revealed that the mutation led to a dysfunction in immune cells, particularly resulting in a deficiency of B cells and other immune components, identifying ezrin deficiency as a new genetic cause for B-cell deficiencies.
Article Abstract
Background: 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.
Methods: Whole-exome sequencing identified a homozygous missense mutation of the gene encoding ezrin (EZR), substituting a threonine for an alanine at position 129.
Results: 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 naive CD4 cells.
Conclusions: Autosomal-recessive human ezrin deficiency is a newly recognized genetic cause of B-cell deficiency affecting cellular and humoral immunity.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11009781 | PMC |
| http://dx.doi.org/10.1016/j.jaci.2023.05.022 | DOI Listing |
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