The Immunopathological Landscape of Human Pre-Tcra Deficiency: From Rare to Common Variants

The Immunopathological Landscape of Human Pre-Tcra Deficiency: From Rare to Common Variants Publisher Pubmed

Materna M^{1, 2} ; Delmonte OM³ ; Bosticardo M³ ; Momenilandi M^{1, 2} ; Conrey PE⁴ ; Muylder BCD⁵ ; Bravetti C^{6, 7} ; Bellworthy R⁸ ; Cederholm A⁹ ; Staels F¹⁰ ; Ganoza CA¹¹ ; Darko S¹² ; Sayed S⁴ ; Floch CL^{1, 2} Show All Authors

Materna M^{1, 2}
Delmonte OM³
Bosticardo M³
Momenilandi M^{1, 2}
Conrey PE⁴
Muylder BCD⁵
Bravetti C^{6, 7}
Bellworthy R⁸
Cederholm A⁹
Staels F¹⁰
Ganoza CA¹¹
Darko S¹²
Sayed S⁴
Floch CL^{1, 2}
Ogishi M¹³
Rinchai D¹³
Guenoun A¹⁴
Bolze A¹⁵
Khan T¹⁶
Gervais A^{1, 2}
Kruger R¹⁷
Voller M¹⁷
Palterer B³
Sadeghishabestari M¹⁸
De Septenville AL⁶
Schramm CA¹²
Shah S¹²
Tellocajiao JJ^{4, 19}
Pala F³
Amini K³
Campos JS⁴
Lima NS¹²
Eriksson D²⁰
Levy R^{1, 2, 21}
Seeleuthner Y^{1, 2}
Jyonouchi S⁴
Ata M¹⁴
Ali FA¹⁴
Deswarte C^{1, 2}
Pereira A^{1, 2}
Megret J²²
Le Voyer T^{1, 2}
Bastard P^{1, 21}
Berteloot L²³
Dussiot M^{2, 24}
Vladikine N^{1, 2}
Cardenas PP²⁵
Jouanguy E¹
Alqahtani M²⁶
Hasan A²⁷
Thanaraj TA²⁸
Rosain J^{1, 2}
Qureshah FA¹³
Sabato V²⁹
Alyanakian MA³⁰
Leruezville M³¹
Rozenberg F³²
Haddad E³³
Regueiro JR²⁵
Toribio ML³⁴
Kelsen JR³⁵
Salehi M^{36, 37}
Nasiri S³⁸
Torabizadeh M³⁹
Roknizadeh H⁴⁰
Changiashtiani M⁴¹
Vatandoost N^{37, 42}
Moravej H⁴³
Akrami SM^{44, 45}
Mazloomrezaei M⁴⁵
Cobat A¹
Meyts I⁴⁶
Toyofuku E⁴⁸
Nishimura M⁴⁹
Moriya K⁵⁰
Mizukami T⁴⁹
Imai K⁵⁰
Abel L¹
Malissen B^{51, 52}
Almulla F²⁸
Alkuraya FS^{26, 53}
Parvaneh N⁵⁴
Von Bernuth H^{17, 55, 56, 57}
Beetz C¹¹
Davi F^{6, 7}
Douek DC¹²
Langlais D⁸
Landegren N^{9, 58}
Marr N^{14, 59}
Morio T⁴⁸
Shahrooei M^{45, 60}
Schrijvers R¹⁰
Henrickson SE^{4, 61, 62}
Luche H⁵²
Notarangelo LD³
Casanova JL^{1, 2, 13, 63, 64}
Beziat V^{2, 13}

Show Affiliations

1. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France
2. Imagine Institute, University of Paris-Cite, Paris, France
3. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
4. Division of Allergy Immunology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
5. University of Paris, Institut Cochin, INSERM U1016, CNRS UMR8104, Paris, France
6. Department of Biological Hematology, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris (AP-HP), Sorbonne Universite, 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, United States
13. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, United States
14. Department of Human Immunology, Sidra Medicine, Doha, Qatar
15. Helix, San Mateo, CA, United States
16. The Jackson Laboratory, Farmington, CT, United States
17. Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charite - Universitatsmedizin Berlin, Freie Universitat Berlin, Humboldt-Universitat zu Berlin, 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, United States
20. Department of Immunology, Genetics and Pathology, Uppsala University, 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, 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, Kuwait City, Dasman, Kuwait
28. Department of Genetics and Bioinformatics, Research Division, Dasman Diabetes Institute, Kuwait City, Dasman, 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-Hopitaux 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 Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autonoma de Madrid (UAM), Madrid, Spain
35. Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
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 NonCommunicable 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 Universite, 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, Charite - Universitatsmedizin Berlin, Berlin, Germany
56. Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charite - Universitatsmedizin 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, United States
62. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
63. Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France
64. Howard Hughes Medical Institute, The Rockefeller University, New York, NY, United States

Source: Science Published:2024

Abstract

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-a T cell receptor (pre-TCRa) expression. Low circulating naive a|! T cell counts at birth persisted over time, with normal memory a|>, and high T5 T cell counts. Their TCRa repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue aft 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 aft T cell counts but high yS T cell counts. Although residual pre-TCRa expression drove the differentiation of more ap T cells, autoimmune conditions were more frequent in these patients compared with the general population. © 2024 American Association for the Advancement of Science. All rights reserved.

2. Human Carmil2 Deficiency Underlies a Broader Immunological and Clinical Phenotype Than Cd28 Deficiency, Journal of Experimental Medicine (2023)

Experts (# of related papers)

Tooba Momen (1)

Style	Citing Format
MLA	Materna M, et al.. "The Immunopathological Landscape of Human Pre-Tcra Deficiency: From Rare to Common Variants." Science, vol. 383, no. 6686, 2024, pp. -.
APA	Materna M, Delmonte OM, Bosticardo M, Momenilandi M, Conrey PE, Muylder BCD, Bravetti C, Bellworthy R, Cederholm A, Staels F, Ganoza CA, Darko S, Sayed S, Floch CL, Ogishi M, Rinchai D, Guenoun A, Bolze A, Khan T, ... Beziat V (2024). The Immunopathological Landscape of Human Pre-Tcra Deficiency: From Rare to Common Variants. Science, 383(6686), -.
Chicago	Materna M, Delmonte OM, Bosticardo M, Momenilandi M, Conrey PE, Muylder BCD, Bravetti C, et al.. "The Immunopathological Landscape of Human Pre-Tcra Deficiency: From Rare to Common Variants." Science 383, no. 6686 (2024): -.
Harvard	Materna M et al. (2024) 'The Immunopathological Landscape of Human Pre-Tcra Deficiency: From Rare to Common Variants', Science, 383(6686), pp. -.
Vancouver	Materna M, Delmonte OM, Bosticardo M, Momenilandi M, Conrey PE, Muylder BCD, et al.. The Immunopathological Landscape of Human Pre-Tcra Deficiency: From Rare to Common Variants. Science. 2024;383(6686):-.
BibTex	@article{ author = {Materna M and Delmonte OM and Bosticardo M and Momenilandi M and Conrey PE and Muylder BCD and Bravetti C and Bellworthy R and Cederholm A and Staels F and Ganoza CA and Darko S and Sayed S and Floch CL and Ogishi M and Rinchai D and Guenoun A and Bolze A and Khan T and Gervais A and Kruger R and Voller M and Palterer B and Sadeghishabestari M and De Septenville AL and Schramm CA and Shah S and Tellocajiao JJ and Pala F and Amini K and Campos JS and Lima NS and Eriksson D and Levy R and Seeleuthner Y and Jyonouchi S and Ata M and Ali FA and Deswarte C and Pereira A and Megret J and Le Voyer T and Bastard P and Berteloot L and Dussiot M and Vladikine N and Cardenas PP and Jouanguy E and Alqahtani M and Hasan A and Thanaraj TA and Rosain J and Qureshah FA and Sabato V and Alyanakian MA and Leruezville M and Rozenberg F and Haddad E and Regueiro JR and Toribio ML and Kelsen JR and Salehi M and Nasiri S and Torabizadeh M and Roknizadeh H and Changiashtiani M and Vatandoost N and Moravej H and Akrami SM and Mazloomrezaei M and Cobat A and Meyts I and Toyofuku E and Nishimura M and Moriya K and Mizukami T and Imai K and Abel L and Malissen B and Almulla F and Alkuraya FS and Parvaneh N and Von Bernuth H and Beetz C and Davi F and Douek DC and Langlais D and Landegren N and Marr N and Morio T and Shahrooei M and Schrijvers R and Henrickson SE and Luche H and Notarangelo LD and Casanova JL and Beziat V}, title = {The Immunopathological Landscape of Human Pre-Tcra Deficiency: From Rare to Common Variants}, journal = {Science}, volume = {383}, number = {6686}, pages = {-}, year = {2024} }
RIS	TY - JOUR AU - Materna M AU - Delmonte OM AU - Bosticardo M AU - Momenilandi M AU - Conrey PE AU - Muylder BCD AU - Bravetti C AU - Bellworthy R AU - Cederholm A AU - Staels F AU - Ganoza CA AU - Darko S AU - Sayed S AU - Floch CL AU - Ogishi M AU - Rinchai D AU - Guenoun A AU - Bolze A AU - Khan T AU - Gervais A AU - Kruger R AU - Voller M AU - Palterer B AU - Sadeghishabestari M AU - De Septenville AL AU - Schramm CA AU - Shah S AU - Tellocajiao JJ AU - Pala F AU - Amini K AU - Campos JS AU - Lima NS AU - Eriksson D AU - Levy R AU - Seeleuthner Y AU - Jyonouchi S AU - Ata M AU - Ali FA AU - Deswarte C AU - Pereira A AU - Megret J AU - Le Voyer T AU - Bastard P AU - Berteloot L AU - Dussiot M AU - Vladikine N AU - Cardenas PP AU - Jouanguy E AU - Alqahtani M AU - Hasan A AU - Thanaraj TA AU - Rosain J AU - Qureshah FA AU - Sabato V AU - Alyanakian MA AU - Leruezville M AU - Rozenberg F AU - Haddad E AU - Regueiro JR AU - Toribio ML AU - Kelsen JR AU - Salehi M AU - Nasiri S AU - Torabizadeh M AU - Roknizadeh H AU - Changiashtiani M AU - Vatandoost N AU - Moravej H AU - Akrami SM AU - Mazloomrezaei M AU - Cobat A AU - Meyts I AU - Toyofuku E AU - Nishimura M AU - Moriya K AU - Mizukami T AU - Imai K AU - Abel L AU - Malissen B AU - Almulla F AU - Alkuraya FS AU - Parvaneh N AU - Von Bernuth H AU - Beetz C AU - Davi F AU - Douek DC AU - Langlais D AU - Landegren N AU - Marr N AU - Morio T AU - Shahrooei M AU - Schrijvers R AU - Henrickson SE AU - Luche H AU - Notarangelo LD AU - Casanova JL AU - Beziat V TI - The Immunopathological Landscape of Human Pre-Tcra Deficiency: From Rare to Common Variants JO - Science VL - 383 IS - 6686 SP - EP - PY - 2024 ER -

Science Communicator Platform

Authors

Authors Affiliations

Abstract