Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia
Abstract Complete tyrosine kinase 2 (TYK2) deficiency has been previously described in patients with primary immunodeficiency diseases. The patients were infected with various pathogens, including mycobacteria and/or viruses, and one of the patients developed hyper-IgE syndrome. A detailed immunolog...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2018
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/c8e265b15bc749268f942c3db043f96f |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:c8e265b15bc749268f942c3db043f96f |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:c8e265b15bc749268f942c3db043f96f2021-12-02T11:41:02ZCompound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia10.1038/s41598-018-25260-82045-2322https://doaj.org/article/c8e265b15bc749268f942c3db043f96f2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25260-8https://doaj.org/toc/2045-2322Abstract Complete tyrosine kinase 2 (TYK2) deficiency has been previously described in patients with primary immunodeficiency diseases. The patients were infected with various pathogens, including mycobacteria and/or viruses, and one of the patients developed hyper-IgE syndrome. A detailed immunological investigation of these patients revealed impaired responses to type I IFN, IL-10, IL-12 and IL-23, which are associated with increased susceptibility to mycobacterial and/or viral infections. Herein, we report a recessive partial TYK2 deficiency in two siblings who presented with T-cell lymphopenia characterized by low naïve CD4+ T-cell counts and who developed Epstein-Barr virus (EBV)-associated B-cell lymphoma. Targeted exome-sequencing of the siblings’ genomes demonstrated that both patients carried novel compound heterozygous mutations (c.209_212delGCTT/c.691C > T, p.Cys70Serfs*21/p.Arg231Trp) in the TYK2. The TYK2 protein levels were reduced by 35% in the T cells of the patient. Unlike the response under complete TYK2 deficiency, the patient’s T cells responded normally to type I IFN, IL-6, IL-10 and IL-12, whereas the cells displayed an impaired response to IL-23. Furthermore, the level of STAT1 was low in the cells of the patient. These studies reveal a new clinical entity of a primary immunodeficiency with T-cell lymphopenia that is associated with compound heterozygous TYK2 mutations in the patients.Michiko NemotoHiroyoshi HattoriNaoko MaedaNobuhiro AkitaHideki MuramatsuSuzuko MoritaniTomonori KawasakiMasami MaejimaHirotaka OdeAtsuko HachiyaWataru SugiuraYoshiyuki YokomakuKeizo HoribeYasumasa IwataniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Michiko Nemoto Hiroyoshi Hattori Naoko Maeda Nobuhiro Akita Hideki Muramatsu Suzuko Moritani Tomonori Kawasaki Masami Maejima Hirotaka Ode Atsuko Hachiya Wataru Sugiura Yoshiyuki Yokomaku Keizo Horibe Yasumasa Iwatani Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia |
| description |
Abstract Complete tyrosine kinase 2 (TYK2) deficiency has been previously described in patients with primary immunodeficiency diseases. The patients were infected with various pathogens, including mycobacteria and/or viruses, and one of the patients developed hyper-IgE syndrome. A detailed immunological investigation of these patients revealed impaired responses to type I IFN, IL-10, IL-12 and IL-23, which are associated with increased susceptibility to mycobacterial and/or viral infections. Herein, we report a recessive partial TYK2 deficiency in two siblings who presented with T-cell lymphopenia characterized by low naïve CD4+ T-cell counts and who developed Epstein-Barr virus (EBV)-associated B-cell lymphoma. Targeted exome-sequencing of the siblings’ genomes demonstrated that both patients carried novel compound heterozygous mutations (c.209_212delGCTT/c.691C > T, p.Cys70Serfs*21/p.Arg231Trp) in the TYK2. The TYK2 protein levels were reduced by 35% in the T cells of the patient. Unlike the response under complete TYK2 deficiency, the patient’s T cells responded normally to type I IFN, IL-6, IL-10 and IL-12, whereas the cells displayed an impaired response to IL-23. Furthermore, the level of STAT1 was low in the cells of the patient. These studies reveal a new clinical entity of a primary immunodeficiency with T-cell lymphopenia that is associated with compound heterozygous TYK2 mutations in the patients. |
| format |
article |
| author |
Michiko Nemoto Hiroyoshi Hattori Naoko Maeda Nobuhiro Akita Hideki Muramatsu Suzuko Moritani Tomonori Kawasaki Masami Maejima Hirotaka Ode Atsuko Hachiya Wataru Sugiura Yoshiyuki Yokomaku Keizo Horibe Yasumasa Iwatani |
| author_facet |
Michiko Nemoto Hiroyoshi Hattori Naoko Maeda Nobuhiro Akita Hideki Muramatsu Suzuko Moritani Tomonori Kawasaki Masami Maejima Hirotaka Ode Atsuko Hachiya Wataru Sugiura Yoshiyuki Yokomaku Keizo Horibe Yasumasa Iwatani |
| author_sort |
Michiko Nemoto |
| title |
Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia |
| title_short |
Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia |
| title_full |
Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia |
| title_fullStr |
Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia |
| title_full_unstemmed |
Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia |
| title_sort |
compound heterozygous tyk2 mutations underlie primary immunodeficiency with t-cell lymphopenia |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/c8e265b15bc749268f942c3db043f96f |
| work_keys_str_mv |
AT michikonemoto compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT hiroyoshihattori compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT naokomaeda compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT nobuhiroakita compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT hidekimuramatsu compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT suzukomoritani compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT tomonorikawasaki compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT masamimaejima compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT hirotakaode compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT atsukohachiya compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT watarusugiura compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT yoshiyukiyokomaku compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT keizohoribe compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia AT yasumasaiwatani compoundheterozygoustyk2mutationsunderlieprimaryimmunodeficiencywithtcelllymphopenia |
| _version_ |
1718395484749430784 |