Title: | The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants |
Journal: | Science |
Published: | 1 Mar 2024 |
Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38422122/ |
DOI: | https://doi.org/10.1126/science.adh4059 |
Title: | The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants |
Journal: | Science |
Published: | 1 Mar 2024 |
Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38422122/ |
DOI: | https://doi.org/10.1126/science.adh4059 |
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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.</p>
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40436 | Prediction models of health and wellness traits based on genetics, anthropometric, and clinical data |
Enabling scientific discoveries that improve human health