RT Journal Article
T1 Study of an extended family with CTLA-4 deficiency suggests a CD28/CTLA-4 independent mechanism responsible for differences in disease manifestations and severity.
A1 Hou, Tie Zheng
A1 Olbrich, Peter
A1 Soto, Jose Manuel Lucena
A1 Sanchez, Berta
A1 Moreno, Paula Sanchez
A1 Borte, Stephan
A1 Stauss, Hans J
A1 Burns, Siobhan O
A1 Walker, Lucy S K
A1 Pan-Hammarström, Qiang
A1 Hammarström, Lennart
A1 Sansom, David M
A1 Neth, Olaf
K1 Autoimmunity
K1 CD28
K1 CTLA-4
K1 Immunodeficiency
K1 Mutation
K1 Regulatory T cells
AB 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.
YR 2018
FD 2018-01-03
LK http://hdl.handle.net/10668/11974
UL http://hdl.handle.net/10668/11974
LA en
DS RISalud
RD Apr 17, 2025