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Title: Study of an extended family with CTLA-4 deficiency suggests a CD28/CTLA-4 independent mechanism responsible for differences in disease manifestations and severity.
Authors: Hou, Tie Zheng
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
Keywords: Autoimmunity;CD28;CTLA-4;Immunodeficiency;Mutation;Regulatory T cells
metadata.dc.subject.mesh: CD28 Antigens
CTLA-4 Antigen
Family Health
Intestinal Diseases
Lymphocyte Activation
Mutation, Missense
Severity of Illness Index
Signal Transduction
T-Lymphocytes, Regulatory
Issue Date: 3-Jan-2018
Abstract: 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.
metadata.dc.identifier.doi: 10.1016/j.clim.2018.01.001
Appears in Collections:Producción 2020

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