A novel ATM mutation associated with elevated atypical lymphocyte populations, hyper-IgM, and cutaneous granulomas

Bibliographische Detailangaben
Veröffentlicht in:	Clinical immunology (Orlando, Fla.). - 1999. - 200(2019) vom: 14. März, Seite 55-63
1. Verfasser:	Minto, Heather (VerfasserIn)
Weitere Verfasser:	Mensah, Kofi A, Reynolds, Paul R, Meffre, Eric, Rubtsova, Kira, Gelfand, Erwin W
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2019
Zugriff auf das übergeordnete Werk:	Clinical immunology (Orlando, Fla.)
Schlagworte:	Case Reports Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Ataxia-telangiectasia CD38(lo)CD21(−/low) B cells Fas Hyper-IgM T-bet Tfh mehr... Tregs γδ T cells Codon, Nonsense ATM protein, human EC 2.7.11.1 Ataxia Telangiectasia Mutated Proteins

Beschreibung
Zusammenfassung:	Copyright © 2019 Elsevier Inc. All rights reserved. Ataxia-Telangiectasia (AT) is an immunodeficiency most often associated with T cell abnormalities. We describe a patient with a hyper-IgM phenotype and immune cell abnormalities that suggest a distinct clinical phenotype. Significant B cell abnormalities with increased unswitched memory B cells, decreased naive transitional B cells, and an elevated frequency of CD19+CD38loCD27-CD10-CD21-/low B cells expressing high levels of T-bet and Fas were demonstrated. The B cells were hyporesponsive to in vitro stimulation through the B cell receptor, Toll like receptors (TLR) 7 and 9, and CD40. T cell homeostasis was also disturbed with a significant increase in γδ T cells, circulating T follicular helper cells (Tfh), and decreased numbers of T regulatory cells. The ATM mutations in this patient are posited to have resulted in the perturbations in the frequencies and distributions of B and T cell subsets, resulting in the phenotype in this patient. KEY MESSAGES: A novel mutation creating a premature stop codon and a nonsense mutation in the ATM gene are postulated to have resulted in the unique clinical picture characterized by abnormal B and T cell populations, lymphocyte subset dysfunction, granuloma formation, and a hyper-IgM phenotype. CAPSULE SUMMARY: A patient presented with ataxia-telangiectasia, cutaneous granulomas, and a hyper-IgM phenotype; a novel combination of mutations in the ATM gene was associated with abnormal distributions, frequencies, and function of T and B lymphocyte subsets
Beschreibung:	Date Completed 31.12.2019 Date Revised 23.04.2024 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-7035
DOI:	10.1016/j.clim.2019.01.002