A novel homozygous mutation in RASGRP1 that predisposes to immune dysregulation and immunodeficiency associated with uncontrolled Epstein-Barr virus-induced B cell proliferation
Copyright © 2023 Elsevier Inc. All rights reserved.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 257(2023) vom: 22. Dez., Seite 109813 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2023
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Case Reports Journal Article Research Support, Non-U.S. Gov't Epstein-Bar virus infections Immune dysregulation Immunodeficiency RASGRP1 deficiency T cell function DNA-Binding Proteins Guanine Nucleotide Exchange Factors |
| Zusammenfassung: | Copyright © 2023 Elsevier Inc. All rights reserved. BACKGROUND: RASGRP1-deficiency results in an immune dysregulation and immunodeficiency that manifest as autoimmunity, lymphoproliferation, lymphopenia, defective T cell function, and increased incidence of Epstein-Bar Virus infections and lymphomas OBJECTIVE: To investigate the mechanism of autoimmune hemolytic anemia and infections in a male patient of consanguineous parents from Lebanon METHODS: Genetic diagnosis was obtained using next generation and Sanger sequencing. Protein expression and phosphorylation were determined by immunoblotting. T and B cell development and function were studied by flow cytometry. Cytokine and immunoglobulin secretions were quantified by enzyme-linked immunosorbent assay RESULTS: The patient suffered from severe lymphopenia especially affecting the T cell compartment. Genetic analysis revealed a homozygous insertion of adenine at position 1396_1397 in RASGRP1 that abolished protein expression and downstream Ras signaling. T cells from the patient showed severe activation defects resulting in uncontrolled Epstein-Bar Virus-induced B cell proliferation. B cells from the patient were normal CONCLUSION: This report expands the spectrum of mutations in patients with RasGRP1 deficiency, and provides evidence for the important role RasGRP1 plays in the ability of T cells to control Epstein-Bar Virus-induced B cell proliferation CLINICAL IMPLICATIONS: Following diagnosis, the patient will be maintained on oral valganciclovir and monitored regularly for Epstein-Bar Virus infections to avoid the development of Epstein-Bar Virus- induced B cell lymphoma. He is also candidate for hematopoietic stem cell transplantation |
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| Beschreibung: | Date Completed 03.01.2024 Date Revised 10.04.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2023.109813 |