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 Lucena-Soto, Jose Manuel
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.
PB Academic Press
YR 2018
FD 2018-03
LK http://hdl.handle.net/10668/11974
UL http://hdl.handle.net/10668/11974
LA en
NO Hou TZ, Olbrich P, Soto JML, Sanchez B, Moreno PS, Borte S, et al. Study of an extended family with CTLA-4 deficiency suggests a CD28/CTLA-4 independent mechanism responsible for differences in disease manifestations and severity. Clin Immunol. 2018 Mar;188:94-102.
DS RISalud
RD Sep 7, 2025