Tuberculosis and impaired IL-23–dependent IFN-γ immunity in humans homozygous for a common TYK2 missense variant

Author:

Boisson-Dupuis Stéphanie123ORCID,Ramirez-Alejo Noe1ORCID,Li Zhi45ORCID,Patin Etienne678ORCID,Rao Geetha9,Kerner Gaspard23ORCID,Lim Che Kang1011,Krementsov Dimitry N.12ORCID,Hernandez Nicholas1,Ma Cindy S.913ORCID,Zhang Qian114ORCID,Markle Janet1ORCID,Martinez-Barricarte Ruben1,Payne Kathryn9ORCID,Fisch Robert1,Deswarte Caroline23,Halpern Joshua1ORCID,Bouaziz Matthieu23,Mulwa Jeanette1,Sivanesan Durga1516,Lazarov Tomi17ORCID,Naves Rodrigo18ORCID,Garcia Patricia19,Itan Yuval12021,Boisson Bertrand123ORCID,Checchi Alix23,Jabot-Hanin Fabienne23,Cobat Aurélie23,Guennoun Andrea14ORCID,Jackson Carolyn C.122ORCID,Pekcan Sevgi23,Caliskaner Zafer24ORCID,Inostroza Jaime25ORCID,Costa-Carvalho Beatriz Tavares26ORCID,de Albuquerque Jose Antonio Tavares27,Garcia-Ortiz Humberto28,Orozco Lorena28,Ozcelik Tayfun29,Abid Ahmed30ORCID,Rhorfi Ismail Abderahmani3031ORCID,Souhi Hicham30ORCID,Amrani Hicham Naji30ORCID,Zegmout Adil30ORCID,Geissmann Frédéric17ORCID,Michnick Stephen W.15,Muller-Fleckenstein Ingrid31,Fleckenstein Bernhard31,Puel Anne123ORCID,Ciancanelli Michael J.1ORCID,Marr Nico14ORCID,Abolhassani Hassan1032ORCID,Balcells María Elvira33ORCID,Condino-Neto Antonio27,Strickler Alexis34ORCID,Abarca Katia35ORCID,Teuscher Cory36,Ochs Hans D.37ORCID,Reisli Ismail38,Sayar Esra H.38,El-Baghdadi Jamila39ORCID,Bustamante Jacinta12340,Hammarström Lennart101141,Tangye Stuart G.913ORCID,Pellegrini Sandra45ORCID,Quintana-Murci Lluis678ORCID,Abel Laurent123ORCID,Casanova Jean-Laurent1234243ORCID

Affiliation:

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

2. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.

3. Paris Descartes University, Imagine Institute, Paris, France.

4. Cytokine Signaling Unit, Pasteur Institute, Paris, France.

5. INSERM U1221, Paris, France.

6. Human Evolutionary Genetics Unit, Pasteur Institute, Paris, France.

7. CNRS UMR2000, Paris, France.

8. Center of Bioinformatics, Biostatistics and Integrative Biology, Pasteur Institute, Paris, France.

9. Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.

10. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.

11. Department of Clinical Translational Research, Singapore General Hospital, Singapore, Singapore.

12. Department of Biomedical and Health Sciences, University of Vermont, Burlington, VT, USA.

13. St. Vincent's Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia.

14. Sidra Medicine, Doha, Qatar.

15. Department of Biochemistry, University of Montreal, Montreal, Quebec, Canada.

16. Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada.

17. Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

18. Institute of Biochemical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.

19. Laboratory of Microbiology, Clinical Laboratory Department School of Medicine, Pontifical Catholic University of Chile, Santiago, Chile.

20. The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

21. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

22. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

23. Department of Pediatric Pulmonology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey.

24. Meram Faculty of Medicine, Department of Internal Medicine, Division of Allergy and Immunology, Necmettin Erbakan University, Konya, Turkey.

25. Jeffrey Modell Center for Diagnosis and Research in Primary Immunodeficiencies, Faculty of Medicine University of La Frontera, Temuco, Chile.

26. Department of Pediatrics, Federal University of São Paulo Medical School, São Paulo, Brazil.

27. Department of Immunology, Institute of Biomedical Sciences, and Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil.

28. National Institute of Genomic Medicine, Mexico City, Mexico.

29. Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.

30. Department of Pneumology, Military Hospital Mohammed V, Rabat, Morocco.

31. Institute of Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany.

32. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

33. Department of Infectious Diseases, Medical School, Pontifical Catholic University of Chile, Santiago, Chile.

34. Department of Pediatrics, San Sebastián University, Santiago, Chile.

35. Department of Infectious Diseases and Pediatric Immunology, School of Medicine, Pontifical Catholic University of Chile, Santiago, Chile.

36. Department of Medicine, Immunobiology Program, University of Vermont, Burlington, VT, USA.

37. Seattle Children's Research Institute and Department of Pediatrics, University of Washington, Seattle, WA, USA.

38. Department of Pediatric Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey.

39. Genetics Unit, Military Hospital Mohamed V, Hay Riad, Rabat, Morocco.

40. Center for the Study of Primary Immunodeficiencies, AP-HP, Necker Hospital for Sick Children, Paris, France.

41. Beijing Genomics Institute BGI-Shenzhen, Shenzhen, China.

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

43. Howard Hughes Medical Institute, New York, NY, USA.

Abstract

Homozygosity for the P1104A missense variant of the TYK2 Janus kinase is common monogenic etiology of primary tuberculosis.

Funder

National Institutes of Health

Agence Nationale de la Recherche

European Research Council

Canadian Institutes of Health Research

National Health and Medical Research Council

Stony Wold-Herbert Fund

Consejo Nacional de Ciencia y Tecnología

Damon Runyon Cancer Research Foundation

GENMSMD

Support of Clinical Research

NSW Department of Health

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine,Immunology

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