| 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 |
Publication 8626
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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.</p>
98 Authors
- Marie Materna
- Ottavia M Delmonte
- Marita Bosticardo
- Mana Momenilandi
- Peyton E Conrey
- Bénédicte Charmeteau-De Muylder
- Clotilde Bravetti
- Rebecca Bellworthy
- Axel Cederholm
- Frederik Staels
- Christian A Ganoza
- Samuel Darko
- Samir Sayed
- Corentin Le Floc'h
- Masato Ogishi
- Darawan Rinchai
- Andrea Guenoun
- Alexandre Bolze
- Taushif Khan
- Adrian Gervais
- Renate Krüger
- Mirjam Völler
- Boaz Palterer
- Mahnaz Sadeghi-Shabestari
- Anne Langlois de Septenville
- Chaim A Schramm
- Sanjana Shah
- John J Tello-Cajiao
- Francesca Pala
- Kayla Amini
- Jose S Campos
- Noemia Santana Lima
- Daniel Eriksson
- Romain Lévy
- Yoann Seeleuthner
- Soma Jyonouchi
- Manar Ata
- Fatima Al Ali
- Caroline Deswarte
- Anaïs Pereira
- Jérôme Mégret
- Tom Le Voyer
- Paul Bastard
- Laureline Berteloot
- Michaël Dussiot
- Natasha Vladikine
- Paula P Cardenas
- Emmanuelle Jouanguy
- Mashael Alqahtani
- Amal Hasan
- Thangavel Alphonse Thanaraj
- Jérémie Rosain
- Fahd Al Qureshah
- Vito Sabato
- Marie Alexandra Alyanakian
- Marianne Leruez-Ville
- Flore Rozenberg
- Elie Haddad
- Jose R Regueiro
- Maria L Toribio
- Judith R Kelsen
- Mansoor Salehi
- Shahram Nasiri
- Mehdi Torabizadeh
- Hassan Rokni-Zadeh
- Majid Changi-Ashtiani
- Nasimeh Vatandoost
- Hossein Moravej
- Seyed Mohammad Akrami
- Mohsen Mazloomrezaei
- Aurélie Cobat
- Isabelle Meyts
- Etsushi Toyofuku
- Madoka Nishimura
- Kunihiko Moriya
- Tomoyuki Mizukami
- Kohsuke Imai
- Laurent Abel
- Bernard Malissen
- Fahd Al-Mulla
- Fowzan Sami Alkuraya
- Nima Parvaneh
- Horst von Bernuth
- Christian Beetz
- Frédéric Davi
- Daniel C Douek
- Rémi Cheynier
- David Langlais
- Nils Landegren
- Nico Marr
- Tomohiro Morio
- Mohammad Shahrooei
- Rik Schrijvers
- Sarah E Henrickson
- Hervé Luche
- Luigi D Notarangelo
- Jean-Laurent Casanova
- Vivien Béziat
1 Application
| Application ID | Title |
|---|---|
| 40436 | Prediction models of health and wellness traits based on genetics, anthropometric, and clinical data |
Enabling scientific discoveries that improve human health