Early-onset pulmonary and cutaneous vasculitis driven by
constitutively active SRC-family kinase HCK

J 2022

Early-onset pulmonary and cutaneous vasculitis driven by constitutively active SRC-family kinase HCK

KANDEROVA, Veronika, Tamara SVOBODOVA, Simon BORNA, Martina FEJTKOVA, Vendula MARTINU et. al.

Základní údaje

Originální název

Early-onset pulmonary and cutaneous vasculitis driven by constitutively active SRC-family kinase HCK

Autoři

Vydání

Journal of allergy and clinical immunology, New York, Mosby-Elsevier, 2022, 0091-6749

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30102 Immunology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 14.200

Kód RIV

RIV/00216224:14740/22:00128769

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1016/j.jaci.2021.07.046

UT WoS

000820784100013

Klíčová slova anglicky

SRC-family kinase; hematopoietic cell kinase; inborn error of immunity; pulmonary hemorrhage; cutaneous vasculitis; autoinflammation; inflammatory cytokines; reactive oxygen species; ruxolitinib

Štítky

ne MU, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 4. 2023 10:44, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Background: Inborn errors of immunity are genetic disorders characterized by various degrees of immune dysregulation that can manifest as immune deficiency, autoimmunity, or autoinflammation. The routine use of next-generation sequencing in the clinic has facilitated the identification of an ever-increasing number of inborn errors of immunity, revealing the roles of immunologically important genes in human pathologies. However, despite this progress, treatment is still extremely challenging. Objective: We sought to report a new monogenic autoinflammatory disorder caused by a de novo activating mutation, p.Tyr515*, in hematopoietic cell kinase (HCK). The disease is characterized by cutaneous vasculitis and chronic pulmonary inflammation that progresses to fibrosis. Methods: Whole-exome sequencing, Sanger sequencing, mass spectrometry, and western blotting were performed to identify and characterize the pathogenic HCK mutation. Dysregulation of mutant HCK was confirmed ex vivo in primary cells and in vitro in transduced cell lines. Results: Mutant HCK lacking the C-terminal inhibitory tyrosine Tyr522 exhibited increased kinase activity and enhanced myeloid cell priming, migration and effector functions, such as production of the inflammatory cytokines IL-1 beta, IL-6, IL-8, and TNF-alpha, and production of reactive oxygen species. These aberrant functions were reflected by inflammatory leukocyte infiltration of the lungs and skin. Moreover, an overview of the clinical course of the disease, including therapies, provides evidence for the therapeutic efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in inflammatory lung disease. Conclusions: We propose HCK-driven pulmonary and cutaneous vasculitis as a novel autoinflammatory disorder of inborn errors of immunity.

Návaznosti

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

KANDEROVA, Veronika, Tamara SVOBODOVA, Simon BORNA, Martina FEJTKOVA, Vendula MARTINU, Jana PADEROVA, Michael SVATON, Jarmila KRALOVA, Eva FRONKOVA, Adam KLOCPERK, Stepanka PRUHOVA, Min Ae LEE-KIRSCH, Ludmila HORNOFOVA, Miroslav KOBLIZEK, Petr NOVAK, Olga ZIMMERMANNOVA, Zuzana PARACKOVA, Anna SEDIVA, Tomas KALINA, Ales JANDA, Jana KAYSEROVA, Marcela DVORAKOVA, Milan MACEK, Petr POHUNEK, Petr SEDLACEK, Ashleigh POH, Matthias ERNST, Tomas BRDICKA, Ondrej HRUSAK a Jan LEBL. Early-onset pulmonary and cutaneous vasculitis driven by constitutively active SRC-family kinase HCK. Journal of allergy and clinical immunology. New York: Mosby-Elsevier, 2022, roč. 149, č. 4, s. 1464-1472, 12 s. ISSN 0091-6749. Dostupné z: https://dx.doi.org/10.1016/j.jaci.2021.07.046.

@article{2262441,
   author = {Kanderova, Veronika and Svobodova, Tamara and Borna, Simon and Fejtkova, Martina and Martinu, Vendula and Paderova, Jana and Svaton, Michael and Kralova, Jarmila and Fronkova, Eva and Klocperk, Adam and Pruhova, Stepanka and LeeandKirsch, Min Ae and Hornofova, Ludmila and Koblizek, Miroslav and Novak, Petr and Zimmermannova, Olga and Parackova, Zuzana and Sediva, Anna and Kalina, Tomas and Janda, Ales and Kayserova, Jana and Dvorakova, Marcela and Macek, Milan and Pohunek, Petr and Sedlacek, Petr and Poh, Ashleigh and Ernst, Matthias and Brdicka, Tomas and Hrusak, Ondrej and Lebl, Jan},
   article_location = {New York},
   article_number = {4},
   doi = {http://dx.doi.org/10.1016/j.jaci.2021.07.046},
   keywords = {SRC-family kinase; hematopoietic cell kinase; inborn error of immunity; pulmonary hemorrhage; cutaneous vasculitis; autoinflammation; inflammatory cytokines; reactive oxygen species; ruxolitinib},
   language = {eng},
   issn = {0091-6749},
   journal = {Journal of allergy and clinical immunology},
   title = {Early-onset pulmonary and cutaneous vasculitis driven by constitutively active SRC-family kinase HCK},
   url = {https://www.sciencedirect.com/science/article/pii/S0091674921013956?via%3Dihub},
   volume = {149},
   year = {2022}
}

TY  - JOUR
ID  - 2262441
AU  - Kanderova, Veronika - Svobodova, Tamara - Borna, Simon - Fejtkova, Martina - Martinu, Vendula - Paderova, Jana - Svaton, Michael - Kralova, Jarmila - Fronkova, Eva - Klocperk, Adam - Pruhova, Stepanka - Lee-Kirsch, Min Ae - Hornofova, Ludmila - Koblizek, Miroslav - Novak, Petr - Zimmermannova, Olga - Parackova, Zuzana - Sediva, Anna - Kalina, Tomas - Janda, Ales - Kayserova, Jana - Dvorakova, Marcela - Macek, Milan - Pohunek, Petr - Sedlacek, Petr - Poh, Ashleigh - Ernst, Matthias - Brdicka, Tomas - Hrusak, Ondrej - Lebl, Jan
PY  - 2022
TI  - Early-onset pulmonary and cutaneous vasculitis driven by constitutively active SRC-family kinase HCK
JF  - Journal of allergy and clinical immunology
VL  - 149
IS  - 4
SP  - 1464-1472
EP  - 1464-1472
PB  - Mosby-Elsevier
SN  - 00916749
KW  - SRC-family kinase
KW  - hematopoietic cell kinase
KW  - inborn error of immunity
KW  - pulmonary hemorrhage
KW  - cutaneous vasculitis
KW  - autoinflammation
KW  - inflammatory cytokines
KW  - reactive oxygen species
KW  - ruxolitinib
UR  - https://www.sciencedirect.com/science/article/pii/S0091674921013956?via%3Dihub
N2  - Background: Inborn errors of immunity are genetic disorders characterized by various degrees of immune dysregulation that can manifest as immune deficiency, autoimmunity, or autoinflammation. The routine use of next-generation sequencing in the clinic has facilitated the identification of an ever-increasing number of inborn errors of immunity, revealing the roles of immunologically important genes in human pathologies. However, despite this progress, treatment is still extremely challenging. Objective: We sought to report a new monogenic autoinflammatory disorder caused by a de novo activating mutation, p.Tyr515*, in hematopoietic cell kinase (HCK). The disease is characterized by cutaneous vasculitis and chronic pulmonary inflammation that progresses to fibrosis. Methods: Whole-exome sequencing, Sanger sequencing, mass spectrometry, and western blotting were performed to identify and characterize the pathogenic HCK mutation. Dysregulation of mutant HCK was confirmed ex vivo in primary cells and in vitro in transduced cell lines. Results: Mutant HCK lacking the C-terminal inhibitory tyrosine Tyr522 exhibited increased kinase activity and enhanced myeloid cell priming, migration and effector functions, such as production of the inflammatory cytokines IL-1 beta, IL-6, IL-8, and TNF-alpha, and production of reactive oxygen species. These aberrant functions were reflected by inflammatory leukocyte infiltration of the lungs and skin. Moreover, an overview of the clinical course of the disease, including therapies, provides evidence for the therapeutic efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in inflammatory lung disease. Conclusions: We propose HCK-driven pulmonary and cutaneous vasculitis as a novel autoinflammatory disorder of inborn errors of immunity.
ER  -

KANDEROVA, Veronika, Tamara SVOBODOVA, Simon BORNA, Martina FEJTKOVA, Vendula MARTINU, Jana PADEROVA, Michael SVATON, Jarmila KRALOVA, Eva FRONKOVA, Adam KLOCPERK, Stepanka PRUHOVA, Min Ae LEE-KIRSCH, Ludmila HORNOFOVA, Miroslav KOBLIZEK, Petr NOVAK, Olga ZIMMERMANNOVA, Zuzana PARACKOVA, Anna SEDIVA, Tomas KALINA, Ales JANDA, Jana KAYSEROVA, Marcela DVORAKOVA, Milan MACEK, Petr POHUNEK, Petr SEDLACEK, Ashleigh POH, Matthias ERNST, Tomas BRDICKA, Ondrej HRUSAK a Jan LEBL. Early-onset pulmonary and cutaneous vasculitis driven by constitutively active SRC-family kinase HCK. \textit{Journal of allergy and clinical immunology}. New York: Mosby-Elsevier, 2022, roč.~149, č.~4, s.~1464-1472, 12 s. ISSN~0091-6749. Dostupné z: https://dx.doi.org/10.1016/j.jaci.2021.07.046.

Podrobný výpis o publikaci