The immunopathological landscape of human pre-TCRα deficiency : From rare to common variants
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:383 |
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| Enthalten in: |
Science (New York, N.Y.) - 383(2024), 6686 vom: 27. März, Seite eadh4059 |
| Sprache: |
Englisch |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 04.03.2024 Date Revised 24.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1126/science.adh4059 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369120426 |
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| 100 | 1 | |a Materna, Marie |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The immunopathological landscape of human pre-TCRα deficiency |b From rare to common variants |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 04.03.2024 | ||
| 500 | |a Date Revised 24.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Receptors, Antigen, T-Cell, alpha-beta |2 NLM | |
| 650 | 7 | |a pre-T cell receptor alpha |2 NLM | |
| 650 | 7 | |a Membrane Glycoproteins |2 NLM | |
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