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The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants.
- Source :
-
Science (New York, N.Y.) [Science] 2024 Mar; Vol. 383 (6686), pp. eadh4059. Date of Electronic Publication: 2024 Mar 01. - Publication Year :
- 2024
-
Abstract
- We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αβ T cell counts at birth persisted over time, with normal memory αβ and high γδ T cell counts. Their TCRα repertoire was biased, which suggests 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 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 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 compared with the general population.
- Subjects :
- Humans
Cell Differentiation
Homozygote
Loss of Function Mutation
Lymphocyte Count
Alleles
Infections immunology
Lymphoproliferative Disorders immunology
Pedigree
Male
Female
Middle Aged
Aged
Aged, 80 and over
Autoimmunity genetics
Intraepithelial Lymphocytes immunology
Receptors, Antigen, T-Cell, alpha-beta genetics
Membrane Glycoproteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 383
- Issue :
- 6686
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 38422122
- Full Text :
- https://doi.org/10.1126/science.adh4059