{"doi":"10.1126/science.adh4059","title":"The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants","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.","journal":"Science","year":2024,"id":419728,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":104168,"name":"Ottavia M. Delmonte","orcid":"0000-0002-4772-0799","position":1,"is_corresponding":false},{"id":281845,"name":"Marita Bosticardo","orcid":"0000-0002-1771-4523","position":2,"is_corresponding":false},{"id":871546,"name":"Mana Momenilandi","orcid":"0000-0002-5340-2762","position":3,"is_corresponding":false},{"id":623350,"name":"Peyton Conrey","orcid":"0000-0001-7766-9878","position":4,"is_corresponding":false},{"id":1210423,"name":"Bénédicte Charmeteau-De Muylder","orcid":null,"position":5,"is_corresponding":false},{"id":1209798,"name":"Clotilde Bravetti","orcid":"0000-0003-1442-8748","position":6,"is_corresponding":false},{"id":1209799,"name":"Rebecca Bellworthy","orcid":"0009-0002-5878-1527","position":7,"is_corresponding":false},{"id":1019802,"name":"Axel Cederholm","orcid":"0009-0006-5973-9637","position":8,"is_corresponding":false},{"id":856431,"name":"Frederik Staels","orcid":"0000-0001-5657-9814","position":9,"is_corresponding":false},{"id":1209800,"name":"Christian A. Ganoza","orcid":"0000-0002-5891-5372","position":10,"is_corresponding":false},{"id":277146,"name":"Samuel Darko","orcid":"0000-0002-9711-8122","position":11,"is_corresponding":false},{"id":262568,"name":"Samir Sayed","orcid":"0000-0003-4981-5721","position":12,"is_corresponding":false},{"id":1028526,"name":"Corentin Le Floc’h","orcid":"0009-0007-0590-0437","position":13,"is_corresponding":false},{"id":104463,"name":"Masato Ogishi","orcid":"0000-0003-2421-7389","position":14,"is_corresponding":false},{"id":646404,"name":"Darawan Rinchai","orcid":"0000-0001-8851-7730","position":15,"is_corresponding":false},{"id":1210424,"name":"Andrea Guenoun","orcid":null,"position":16,"is_corresponding":false},{"id":104166,"name":"Alexandre Bolze","orcid":"0000-0001-7399-2766","position":17,"is_corresponding":false},{"id":104489,"name":"Taushif Khan","orcid":"0000-0002-7917-8965","position":18,"is_corresponding":false},{"id":615375,"name":"Adrian Gervais","orcid":"0000-0002-1083-5787","position":19,"is_corresponding":false},{"id":281904,"name":"Renate Krüger","orcid":"0000-0001-8728-9385","position":20,"is_corresponding":false},{"id":1210425,"name":"Mirjam Völler","orcid":null,"position":21,"is_corresponding":false},{"id":391316,"name":"Boaz Palterer","orcid":"0000-0003-2499-8250","position":22,"is_corresponding":false},{"id":1209801,"name":"Mahnaz Sadeghi‐Shabestari","orcid":"0000-0001-5356-3163","position":23,"is_corresponding":false},{"id":1210426,"name":"Anne Langlois de Septenville","orcid":null,"position":24,"is_corresponding":false},{"id":283220,"name":"Chaim A. Schramm","orcid":null,"position":25,"is_corresponding":false},{"id":430140,"name":"Sanjana Shah","orcid":"0000-0002-7389-328X","position":26,"is_corresponding":false},{"id":915571,"name":"John James Tello Cajiao","orcid":"0000-0002-7927-9467","position":27,"is_corresponding":false},{"id":281846,"name":"Francesca Pala","orcid":"0000-0003-4537-9061","position":28,"is_corresponding":false},{"id":1209802,"name":"Kayla Amini","orcid":"0009-0006-7911-1097","position":29,"is_corresponding":false},{"id":711106,"name":"Jose Campos","orcid":"0000-0003-3344-7733","position":30,"is_corresponding":false},{"id":452996,"name":"Noemia S. Lima","orcid":"0000-0003-4399-487X","position":31,"is_corresponding":false},{"id":1019805,"name":"Daniel Eriksson","orcid":"0000-0001-5473-3312","position":32,"is_corresponding":false},{"id":273547,"name":"Romain Lévy","orcid":"0000-0002-6393-0198","position":33,"is_corresponding":false},{"id":104164,"name":"Yoann Seeleuthner","orcid":"0000-0002-1878-8567","position":34,"is_corresponding":false},{"id":283583,"name":"Soma Jyonouchi","orcid":null,"position":35,"is_corresponding":false},{"id":617497,"name":"Manar Ata","orcid":"0000-0001-7111-5719","position":36,"is_corresponding":false},{"id":263165,"name":"Fatima Al Ali","orcid":"0000-0001-6451-7357","position":37,"is_corresponding":false},{"id":263166,"name":"Caroline Deswarte","orcid":"0000-0002-8775-3368","position":38,"is_corresponding":false},{"id":1209803,"name":"A B Pereira","orcid":"0000-0001-5821-5133","position":39,"is_corresponding":false},{"id":883876,"name":"Jérôme Megret","orcid":null,"position":40,"is_corresponding":false},{"id":104488,"name":"Tom Le Voyer","orcid":"0000-0002-0630-8626","position":41,"is_corresponding":false},{"id":104138,"name":"Paul Bastard","orcid":"0000-0002-5926-8437","position":42,"is_corresponding":false},{"id":642456,"name":"Laureline Berteloot","orcid":"0000-0001-9681-3142","position":43,"is_corresponding":false},{"id":317744,"name":"Michaël Dussiot","orcid":"0000-0002-6804-1621","position":44,"is_corresponding":false},{"id":274471,"name":"Natasha Vladikine","orcid":"0000-0002-0607-9202","position":45,"is_corresponding":false},{"id":1209804,"name":"Paula P. Cárdenas","orcid":"0000-0001-9054-8130","position":46,"is_corresponding":false},{"id":104229,"name":"Emmanuelle Jouanguy","orcid":"0000-0002-7358-9157","position":47,"is_corresponding":false},{"id":509557,"name":"Mashael Alqahtani","orcid":"0000-0003-1582-2878","position":48,"is_corresponding":false},{"id":1209805,"name":"Amal Hasan","orcid":"0000-0002-1793-7794","position":49,"is_corresponding":false},{"id":1197395,"name":"Thangavel Alphonse Thanaraj","orcid":"0000-0002-4574-5343","position":50,"is_corresponding":false},{"id":104146,"name":"Jérémie Rosain","orcid":"0000-0002-2822-161X","position":51,"is_corresponding":false},{"id":730018,"name":"Fahd Al Qureshah","orcid":"0000-0002-5022-9917","position":52,"is_corresponding":false},{"id":670402,"name":"Vito Sabato","orcid":"0000-0002-1321-314X","position":53,"is_corresponding":false},{"id":1210427,"name":"Marie Alexandra Alyanakian","orcid":null,"position":54,"is_corresponding":false},{"id":1209806,"name":"Marianne Leruez‐Ville","orcid":"0000-0001-7513-7894","position":55,"is_corresponding":false},{"id":263171,"name":"Flore Rozenberg","orcid":"0000-0001-7212-2021","position":56,"is_corresponding":false},{"id":241578,"name":"Élie Haddad","orcid":"0000-0003-2446-6879","position":57,"is_corresponding":false},{"id":733721,"name":"José R. Regueiro","orcid":"0000-0001-8442-7762","position":58,"is_corresponding":false},{"id":1196034,"name":"Marı́a L. Toribio","orcid":"0000-0002-8637-0373","position":59,"is_corresponding":false},{"id":287831,"name":"Judith R. Kelsen","orcid":"0000-0003-0038-318X","position":60,"is_corresponding":false},{"id":1209807,"name":"Mansoor Salehi","orcid":"0000-0002-6565-0907","position":61,"is_corresponding":false},{"id":1210428,"name":"Shahram Nasiri","orcid":null,"position":62,"is_corresponding":false},{"id":1209808,"name":"Mehdi Torabizadeh","orcid":"0000-0003-3729-763X","position":63,"is_corresponding":false},{"id":1019451,"name":"Hassan Rokni‐Zadeh","orcid":"0000-0001-5503-0344","position":64,"is_corresponding":false},{"id":1019452,"name":"Majid Changi‐Ashtiani","orcid":"0000-0001-6428-9323","position":65,"is_corresponding":false},{"id":1209809,"name":"Nasimeh Vatandoost","orcid":"0000-0003-0189-7529","position":66,"is_corresponding":false},{"id":1210429,"name":"Hossein Moravej","orcid":null,"position":67,"is_corresponding":false},{"id":1209810,"name":"Seyed Mohammad Akrami","orcid":"0000-0003-0169-0202","position":68,"is_corresponding":false},{"id":1028531,"name":"Mohsen Mazloomrezaei","orcid":"0000-0002-9296-9876","position":69,"is_corresponding":false},{"id":57371,"name":"Aurélie Cobat","orcid":"0000-0001-7209-6257","position":70,"is_corresponding":false},{"id":241316,"name":"Isabelle Meyts","orcid":"0000-0003-1214-0302","position":71,"is_corresponding":false},{"id":1210430,"name":"Etsushi Toyofuku","orcid":null,"position":72,"is_corresponding":false},{"id":1209811,"name":"Madoka Nishimura","orcid":"0009-0007-6030-8567","position":73,"is_corresponding":false},{"id":670958,"name":"Kunihiko Moriya","orcid":"0000-0002-0418-5132","position":74,"is_corresponding":false},{"id":1110714,"name":"Tomoyuki Mizukami","orcid":"0000-0002-2508-2810","position":75,"is_corresponding":false},{"id":649222,"name":"Kohsuke Imai","orcid":"0000-0003-2132-8403","position":76,"is_corresponding":false},{"id":241301,"name":"Laurent Abel","orcid":"0000-0001-7016-6493","position":77,"is_corresponding":false},{"id":267607,"name":"Bernard MALISSEN","orcid":"0000-0003-1340-9342","position":78,"is_corresponding":false},{"id":104495,"name":"Fahd Al‐Mulla","orcid":"0000-0001-5409-3829","position":79,"is_corresponding":false},{"id":291081,"name":"Fowzan S. Alkuraya","orcid":"0000-0003-4158-341X","position":80,"is_corresponding":false},{"id":670967,"name":"Nima Parvaneh","orcid":"0000-0002-3397-9716","position":81,"is_corresponding":false},{"id":241324,"name":"Horst von Bernuth","orcid":"0000-0002-5812-7675","position":82,"is_corresponding":false},{"id":325979,"name":"Christian Beetz","orcid":"0000-0001-7061-2895","position":83,"is_corresponding":false},{"id":976662,"name":"Frédéric Davi","orcid":"0000-0002-3764-063X","position":84,"is_corresponding":false},{"id":277153,"name":"Daniel C. Douek","orcid":"0000-0001-5575-8634","position":85,"is_corresponding":false},{"id":1147703,"name":"Rémi Cheynier","orcid":"0000-0003-1146-660X","position":86,"is_corresponding":false},{"id":558864,"name":"David Langlais","orcid":"0000-0003-4429-0110","position":87,"is_corresponding":false},{"id":853499,"name":"Nils Landegren","orcid":"0000-0002-6163-9540","position":88,"is_corresponding":false},{"id":263173,"name":"Nico Marr","orcid":"0000-0002-1927-7072","position":89,"is_corresponding":false},{"id":57372,"name":"Tomohiro Morio","orcid":"0000-0002-9259-1025","position":90,"is_corresponding":false},{"id":104491,"name":"Mohammad Shahrooei","orcid":"0000-0002-4974-3441","position":91,"is_corresponding":false},{"id":618962,"name":"Rik Schrijvers","orcid":"0000-0002-4261-6220","position":92,"is_corresponding":false},{"id":250865,"name":"Sarah E. Henrickson","orcid":"0000-0001-5569-4132","position":93,"is_corresponding":false},{"id":1209812,"name":"Hervé Luche","orcid":"0000-0003-4309-8338","position":94,"is_corresponding":false},{"id":231247,"name":"Luigi D. Notarangelo","orcid":"0000-0002-8335-0262","position":95,"is_corresponding":false},{"id":57373,"name":"Jean-Laurent Casanova","orcid":"0000-0002-7782-4169","position":96,"is_corresponding":false},{"id":104147,"name":"Vivien Béziat","orcid":"0000-0002-4020-824X","position":97,"is_corresponding":false},{"id":274463,"name":"Marie Materna","orcid":"0000-0003-2145-5285","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T01:57:19.937291Z","pmid":"38422122","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}