RT Journal Article
T1 The immunopathological landscape of human pre-TCRα deficiency: from rare to common variants
A1 Materna, Marie
A1 Cárdenas Mastrascusa, Paula Patricia
A1 Regueiro González-Barros, José Ramón
A1 Béziat, Vivien
AB We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-TCRα expression. Low circulating naïve αβ T cell counts at birth persisted over time, with normal memory αβ and high γδ T cell counts. Their TCRα repertoire was biased, suggesting that noncanonical thymic differentiation pathways can rescue αβ T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We alsoreport that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naïve αβ T cell counts but high γδ T cell counts. Although residual pre-TCRα expression drove the differentiation of more αβ T cells, autoimmune conditions were more frequent in these patients than in the general population.
PB American Association for the Advancement of Science
SN 0036-8075
YR 2024
FD 2024-03-22
LK https://hdl.handle.net/20.500.14352/107408
UL https://hdl.handle.net/20.500.14352/107408
LA eng
NO Marie Materna et al. ,The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants.Science383,eadh4059(2024).DOI:10.1126/science.adh4059
NO French National Research Agency
NO Unión Europea
DS Docta Complutense
RD 9 abr 2025