The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants.
Science
; 383(6686): eadh4059, 2024 03.
Article
em En
| MEDLINE
| ID: mdl-38422122
ABSTRACT
We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αß T cell counts at birth persisted over time, with normal memory αß and high γδ T cell counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue αß T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive αß T cell counts but high γδ T cell counts. Although residual pre-TCRα expression drove the differentiation of more αß T cells, autoimmune conditions were more frequent in these patients compared with the general population.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
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Autoimunidade
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Receptores de Antígenos de Linfócitos T alfa-beta
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Linfócitos Intraepiteliais
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Science
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França