The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants.

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

Source :

2024 Mar 1

Pmid / DOI:

38422122

Abstract

We describe humans with rare biallelic loss-of-function 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 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.

Voir la publication

Toutes les publications