Document Type
Article
Publication Date
3-1-2024
Original Citation
Materna M,
Delmonte O,
Bosticardo M,
Momenilandi M,
Conrey P,
Charmeteau-De Muylder B,
Bravetti C,
Bellworthy R,
Cederholm A,
Staels F,
Ganoza C,
Darko S,
Sayed S,
Le Floc'h C,
Ogishi M,
Rinchai D,
Guenoun A,
Bolze A,
Khan T,
Gervais A,
Krüger R,
Völler M,
Palterer B,
Sadeghi-Shabestari M,
Langlois de Septenville A,
Schramm C,
Shah S,
Tello-Cajiao J,
Pala F,
Amini K,
Campos J,
Lima N,
Eriksson D,
Lévy R,
Seeleuthner Y,
Jyonouchi S,
Ata M,
Al Ali F,
Stittrich A,
Deswarte C,
Pereira A,
Mégret J,
Le Voyer T,
Bastard P,
Berteloot L,
Dussiot M,
Vladikine N,
Cardenas P,
Jouanguy E,
Alqahtani M,
Hasan A,
Thanaraj T,
Rosain J,
Al Qureshah F,
Sabato V,
Alyanakian M,
Leruez-Ville M,
Rozenberg F,
Haddad E,
Regueiro J,
Toribio M,
Kelsen J,
Salehi M,
Nasiri S,
Torabizadeh M,
Rokni-Zadeh H,
Changi-Ashtiani M,
Vatandoost N,
Moravej H,
Akrami S,
Mazloomrezaei M,
Cobat A,
Meyts I,
Toyofuku E,
Nishimura M,
Moriya K,
Mizukami T,
Imai K,
Abel L,
Malissen B,
Al-Mulla F,
Alkuraya F,
Parvaneh N,
von Bernuth H,
Beetz C,
Davi F,
Douek D,
Cheynier R,
Langlais D,
Landegren N,
Marr N,
Morio T,
Shahrooei M,
Schrijvers R,
Henrickson S,
Luche H,
Notarangelo L,
Casanova J,
Béziat V.
The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants. Science. 2024;383(6686):eadh4059
Keywords
JGM, Humans, Autoimmunity, Cell Differentiation, Homozygote, Intraepithelial Lymphocytes, Receptors, Antigen, T-Cell, alpha-beta, Membrane Glycoproteins, Loss of Function Mutation, Lymphocyte Count, Alleles, Infections, Lymphoproliferative Disorders, Pedigree, Male, Female, Middle Aged, Aged, Aged, 80 and over
JAX Source
Science. 2024;383(6686):eadh4059
ISSN
1095-9203
PMID
38422122
DOI
https://doi.org/10.1126/science.adh4059
Abstract
We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre–a T cell receptor (pre-TCRa) expression. Low circulating naive ab T cell counts at birth persisted over time, with normal memory ab and high gd T cell counts. Their TCRa repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue ab 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 ab T cell counts but high gd T cell counts. Although residual pre-TCRa expression drove the differentiation of more ab T cells, autoimmune conditions were more frequent in these patients compared with the general population.
Comments
Copyright © 2024 the authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original US government works. https://www. science.org/about/science-licenses-journal-article-reuse. This research was funded in part by the French National Research Agency (ANR) (ANR-10-IAHU-01, ANR-10-LABX-62-IBEID, and ANR-21-CE15- 0034) and the Horizon Europe Framework Programme (HORIZON) (01057100; UNDINE), cOAlition S organizations. This article is also subject to HHMI’s Open Access to Publications policy. HHMI lab heads have previously granted a nonexclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the Author Accepted Manuscript (AAM) of this article can be made freely available under a CC BY 4.0 license immediately upon publication.