The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants
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Materna, Marie | Delmonte, Ottavia, M | Bosticardo, Marita | Momenilandi, Mana | Conrey, Peyton, E | Charmeteau-de Muylder, Bénédicte | Bravetti, Clotilde | Bellworthy, Rebecca | Cederholm, Axel | Staels, Frederik | Ganoza, Christian, A | Darko, Samuel | Sayed, Samir | Le Floc’h, Corentin | Ogishi, Masato | Rinchai, Darawan | Guenoun, Andrea | Bolze, Alexandre | Khan, Taushif | Gervais, Adrian | Krüger, Renate | Völler, Mirjam | Palterer, Boaz | Sadeghi-Shabestari, Mahnaz | Langlois de Septenville, Anne | Schramm, Chaim, A | Shah, Sanjana | Tello-Cajiao, John, J | Pala, Francesca | Amini, Kayla | Campos, Jose, S | Lima, Noemia Santana | Eriksson, Daniel | Lévy, Romain | Seeleuthner, Yoann | Jyonouchi, Soma | Ata, Manar | Al Ali, Fatima | Deswarte, Caroline | Pereira, Anaïs | Mégret, Jérôme | Le Voyer, Tom | Bastard, Paul | Berteloot, Laureline | Dussiot, Michaël | Vladikine, Natasha | Cardenas, Paula, P | Jouanguy, Emmanuelle | Alqahtani, Mashael | Hasan, Amal | Thanaraj, Thangavel Alphonse | Rosain, Jérémie | Al Qureshah, Fahd | Sabato, Vito | Alyanakian, Marie Alexandra | Leruez-Ville, Marianne | Rozenberg, Flore | Haddad, Elie | Regueiro, Jose, R | Toribio, Maria, L | Kelsen, Judith, R | Salehi, Mansoor | Nasiri, Shahram | Torabizadeh, Mehdi | Rokni-Zadeh, Hassan | Changi-Ashtiani, Majid | Vatandoost, Nasimeh | Moravej, Hossein | Akrami, Seyed Mohammad | Mazloomrezaei, Mohsen | Cobat, Aurélie | Meyts, Isabelle | Toyofuku, Etsushi | Nishimura, Madoka | Moriya, Kunihiko | Mizukami, Tomoyuki | Imai, Kohsuke | Abel, Laurent | Malissen, Bernard | Al-Mulla, Fahd | Alkuraya, Fowzan Sami | Parvaneh, Nima | von Bernuth, Horst | Beetz, Christian | Davi, Frédéric | Douek, Daniel, C | Cheynier, Rémi | Langlais, David | Landegren, Nils | Marr, Nico | Morio, Tomohiro | Shahrooei, Mohammad | Schrijvers, Rik | Henrickson, Sarah, E | Luche, Hervé | Notarangelo, Luigi, D | Casanova, Jean-Laurent | Béziat, Vivien
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CCSD ; American Association for the Advancement of Science (AAAS) -
International audience.
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.
