The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants-Reference-Cited by-同舟云学术

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

Published:2024-03 Issue:6686 Volume:383 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Materna Marie¹²^ORCID,Delmonte Ottavia M.³^ORCID,Bosticardo Marita³^ORCID,Momenilandi Mana¹²^ORCID,Conrey Peyton E.⁴^ORCID,Charmeteau-De Muylder Bénédicte⁵,Bravetti Clotilde⁶⁷,Bellworthy Rebecca⁸^ORCID,Cederholm Axel⁹^ORCID,Staels Frederik¹⁰,Ganoza Christian A.¹¹^ORCID,Darko Samuel¹²^ORCID,Sayed Samir⁴^ORCID,Le Floc’h Corentin¹²^ORCID,Ogishi Masato¹³^ORCID,Rinchai Darawan¹³^ORCID,Guenoun Andrea¹⁴^ORCID,Bolze Alexandre¹⁵^ORCID,Khan Taushif¹⁴¹⁶^ORCID,Gervais Adrian¹²^ORCID,Krüger Renate¹⁷,Völler Mirjam¹⁷^ORCID,Palterer Boaz³^ORCID,Sadeghi-Shabestari Mahnaz¹⁸^ORCID,Langlois de Septenville Anne⁶,Schramm Chaim A.¹²,Shah Sanjana¹²,Tello-Cajiao John J.⁴¹⁹^ORCID,Pala Francesca³^ORCID,Amini Kayla³^ORCID,Campos Jose S.⁴^ORCID,Lima Noemia Santana¹²^ORCID,Eriksson Daniel²⁰^ORCID,Lévy Romain¹²²¹^ORCID,Seeleuthner Yoann¹²,Jyonouchi Soma⁴,Ata Manar¹⁴^ORCID,Al Ali Fatima¹⁴^ORCID,Deswarte Caroline¹²^ORCID,Pereira Anaïs¹²^ORCID,Mégret Jérôme²²,Le Voyer Tom¹²^ORCID,Bastard Paul¹²¹³²¹^ORCID,Berteloot Laureline²³^ORCID,Dussiot Michaël²²⁴,Vladikine Natasha¹²,Cardenas Paula P.²⁵^ORCID,Jouanguy Emmanuelle¹²¹³^ORCID,Alqahtani Mashael²⁶,Hasan Amal²⁷^ORCID,Thanaraj Thangavel Alphonse²⁸^ORCID,Rosain Jérémie¹²^ORCID,Al Qureshah Fahd¹³^ORCID,Sabato Vito²⁹,Alyanakian Marie Alexandra³⁰,Leruez-Ville Marianne³¹^ORCID,Rozenberg Flore⁵³²,Haddad Elie³³^ORCID,Regueiro Jose R.²⁵^ORCID,Toribio Maria L.³⁴^ORCID,Kelsen Judith R.³⁵^ORCID,Salehi Mansoor³⁶³⁷^ORCID,Nasiri Shahram³⁸,Torabizadeh Mehdi³⁹,Rokni-Zadeh Hassan⁴⁰^ORCID,Changi-Ashtiani Majid⁴¹^ORCID,Vatandoost Nasimeh³⁷⁴²^ORCID,Moravej Hossein⁴³,Akrami Seyed Mohammad⁴⁴⁴⁵^ORCID,Mazloomrezaei Mohsen⁴⁵^ORCID,Cobat Aurélie¹²¹³^ORCID,Meyts Isabelle⁴⁶⁴⁷^ORCID,Toyofuku Etsushi⁴⁸,Nishimura Madoka⁴⁹^ORCID,Moriya Kunihiko⁵⁰^ORCID,Mizukami Tomoyuki⁴⁹^ORCID,Imai Kohsuke⁵⁰^ORCID,Abel Laurent¹²¹³^ORCID,Malissen Bernard⁵¹⁵²^ORCID,Al-Mulla Fahd²⁸^ORCID,Alkuraya Fowzan Sami²⁶⁵³^ORCID,Parvaneh Nima⁵⁴^ORCID,von Bernuth Horst¹⁷⁵⁵⁵⁶⁵⁷^ORCID,Beetz Christian¹¹,Davi Frédéric⁶⁷,Douek Daniel C.¹²,Cheynier Rémi⁵^ORCID,Langlais David⁸^ORCID,Landegren Nils⁹⁵⁸,Marr Nico¹⁴⁵⁹^ORCID,Morio Tomohiro⁴⁸^ORCID,Shahrooei Mohammad⁴⁵⁶⁰,Schrijvers Rik¹⁰^ORCID,Henrickson Sarah E.⁴⁶¹⁶²^ORCID,Luche Hervé⁵²^ORCID,Notarangelo Luigi D.³^ORCID,Casanova Jean-Laurent¹²¹³⁶³⁶⁴^ORCID,Béziat Vivien¹²¹³^ORCID

Affiliation:

1. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France.

2. Imagine Institute, University of Paris-Cité, Paris, France.

3. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

4. Division of Allergy Immunology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA.

5. University of Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France.

6. Department of Biological Hematology, Hôpital Pitié-Salpêtrière, Assistance Publique–Hôpitaux de Paris (AP-HP) and Sorbonne Université, Paris, France.

7. Sorbonne University, Paris Cancer Institute CURAMUS, INSERM U1138, Paris, France.

8. Deptartment of Human Genetics, Dahdaleh Institute of Genomic Medicine, McGill University, Montreal, QC, Canada.

9. Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.

10. Allergy and Clinical Immunology Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.

11. Centogene GmbH, Rostock, Germany.

12. Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

13. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.

14. Department of Human Immunology, Sidra Medicine, Doha, Qatar.

15. Helix, San Mateo, CA, USA.

16. The Jackson Laboratory, Farmington, CT, USA.

17. Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.

18. Immunology Research Center, TB and Lung Disease Research Center, Mardaniazar Children Hospital, Tabriz University of Medical Science, Tabriz, Iran.

19. Department of Pathology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA.

20. Department of Immunology, Genetics and Pathology, Uppsala University and University Hospital, Section of Clinical Genetics, Uppsala, Sweden.

21. Pediatric Immunology, Hematology and Rheumatology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France.

22. Cytometry Core Facility, SFR Necker, INSERM US24-CNRS UAR3633, Paris, France.

23. Department of Pediatric Radiology, University Hospital Necker-Enfants Malades, AP-HP, Paris, France.

24. Laboratory of Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, INSERM UMR 1163, Paris, France.

25. Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine and 12 de Octubre Health Research Institute (imas12), Madrid, Spain.

26. Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

27. Department of Translational Research, Research Division, Dasman Diabetes Institute, Dasman, Kuwait City, Kuwait.

28. Department of Genetics and Bioinformatics, Research Division, Dasman Diabetes Institute, Dasman, Kuwait City, Kuwait.

29. Department of Immunology, Allergology and Rheumatology, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium.

30. Immunology Laboratory, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

31. Necker Hospital for Sick Children, AP-HP, Paris, France.

32. Virology, Cochin Hospital, AP-HP, APHP-CUP, Paris, France.

33. Department of Pediatrics, Department of Microbiology, Immunology and Infectious Diseases, University of Montreal, CHU Sainte-Justine, Montreal, QC, Canada.

34. Immune System Development and Function Unit, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain.

35. Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA.

36. Cellular, Molecular and Genetics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

37. Department of Genetics and Molecular Biology, Medical School, Isfahan University of Medical Sciences, Isfahan, Iran.

38. Department of Pediatric Neurology, Children’s Medical Center of Abuzar, Jundishapur University of Medical Sciences, Ahvaz, Iran.

39. Golestan Hospital Clinical Research Development Unit, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

40. Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences (ZUMS), Zanjan, Iran.

41. School of Mathematics, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.

42. Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.

43. Neonatal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

44. Medical Genetics Poursina St., Genetic Department, Medical Faculty, Tehran University of Medical Sciences, Tehran, Iran.

45. Dr. Shahrooei Laboratory, Tehran, Iran.

46. Laboratory for Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, Department of Pediatrics, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

47. Department of Pediatrics, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

48. Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.

49. Department of Pediatrics, NHO Kumamoto Medical Center, Kumamoto, Japan.

50. Department of Pediatrics, National Defense Medical College, Saitama, Japan.

51. Immunology Center of Marseille-Luminy, Aix Marseille University, Inserm, CNRS, Marseille, France.

52. Immunophenomics Center (CIPHE), Aix Marseille Université, Inserm, CNRS, Marseille, France.

53. Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

54. Division of Allergy and Clinical Immunology, Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran.

55. Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany.

56. Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany.

57. Labor Berlin GmbH, Department of Immunology, Berlin, Germany.

58. Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden.

59. College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.

60. Clinical and Diagnostic Immunology, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.

61. Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

62. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

63. Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France.

64. Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adh4059

Reference86 articles.

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