Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3

Author:

Haapaniemi Emma M.1,Kaustio Meri2,Rajala Hanna L. M.3,van Adrichem Arjan J.2,Kainulainen Leena4,Glumoff Virpi5,Doffinger Rainer6,Kuusanmäki Heikki2,Heiskanen-Kosma Tarja7,Trotta Luca2,Chiang Samuel8,Kulmala Petri59,Eldfors Samuli2,Katainen Riku10,Siitonen Sanna11,Karjalainen-Lindsberg Marja-Liisa11,Kovanen Panu E.12,Otonkoski Timo1314,Porkka Kimmo3,Heiskanen Kaarina15,Hänninen Arno16,Bryceson Yenan T.8,Uusitalo-Seppälä Raija17,Saarela Janna2,Seppänen Mikko18,Mustjoki Satu3,Kere Juha119

Affiliation:

1. Folkhälsan Institute of Genetics and Research Programs Unit, Molecular Neurology, and

2. Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland;

3. Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki and Helsinki University Central Hospital Cancer Center, Helsinki, Finland;

4. Department of Pediatrics and Department of Medicine, Turku University Hospital, Turku, Finland;

5. Department of Medical Microbiology and Immunology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland;

6. Department of Clinical Biochemistry and Immunology, Addenbrooke’s Hospital and National Institute for Health Research, Cambridge Biomedical Research Center, Cambridge, United Kingdom;

7. Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland;

8. Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;

9. Department of Pediatrics, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland;

10. Department of Medical Genetics, Genome-Scale Biology Research Program, Institute of Biomedicine, University of Helsinki, Helsinki, Finland;

11. Laboratory Services (Hospital District of Helsinki and Uusimaa Laboratory),

12. Department of Pathology, and

13. Children’s Hospital, Helsinki University Central Hospital, Helsinki, Finland;

14. Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland;

15. Children’s Hospital, Helsinki University Central Hospital, Helsinki, Finland,

16. Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland;

17. Department of Infectious Diseases, Satakunta Central Hospital, Pori, Finland;

18. Immunodeficiency Unit, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; and

19. Department of Biosciences and Nutrition, and Center for Innovative Medicine, Karolinska Institutet, Stockholm, Sweden

Abstract

Key Points Germline activating STAT3 mutations were detected in 3 patients with autoimmunity, hypogammaglobulinemia, and mycobacterial disease. T-cell lymphoproliferation, deficiency of regulatory and helper 17 T cells, natural killer cells, dendritic cells, and eosinophils were common.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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