Study of an extended family with CTLA-4 deficiency suggests a CD28/CTLA-4 independent mechanism responsible for differences in disease manifestations and severity

Study of an extended family with CTLA-4 deficiency suggests a CD28/CTLA-4 independent mechanism responsible for differences in disease manifestations and severity

Copyright © 2018 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 188(2018) vom: 01. März, Seite 94-102
1. Verfasser: Hou, Tie Zheng (VerfasserIn)
Weitere Verfasser: Olbrich, Peter, Soto, Jose Manuel Lucena, Sanchez, Berta, Moreno, Paula Sanchez, Borte, Stephan, Stauss, Hans J, Burns, Siobhan O, Walker, Lucy S K, Pan-Hammarström, Qiang, Hammarström, Lennart, Sansom, David M, Neth, Olaf
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2018
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Autoimmunity CD28 CTLA-4 Immunodeficiency Mutation Regulatory T cells CD28 Antigens CTLA-4 Antigen CTLA4 protein, human
Beschreibung
Zusammenfassung:Copyright © 2018 Elsevier Inc. All rights reserved.
The CTLA-4 checkpoint regulates the activation of T cells. Individuals with heterozygous mutations in CTLA-4 have a complex phenotype typically characterized by antibody deficiency alongside variable autoimmunity. Despite severe disease in some individuals, others remain largely unaffected with reasons for this variation unknown. We studied a large family carrying a single point mutation in CTLA-4 leading to an amino acid change R75W and compared both unaffected with affected individuals. We measured a variety of features pertaining to T cell and CTLA-4 biology and observed that at the cellular level there was complete penetrance of CTLA-4 mutations. Accordingly, unaffected individuals were indistinguishable from those with disease in terms of level of CTLA-4 expression, percentage of Treg, upregulation of CTLA-4 upon stimulation and proliferation of CD4 T cells. We conclude that the wide variation in disease phenotype is influenced by immune variation outside of CTLA-4 biology
Beschreibung:Date Completed 22.04.2019
Date Revised 29.01.2022
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2018.01.001