Myeloid lineage cells evince distinct steady-state level of
certain gene groups in dependence on hereditary angioedema
severity

J 2023

Myeloid lineage cells evince distinct steady-state level of certain gene groups in dependence on hereditary angioedema severity

BALLONOVÁ, Lucie, Přemysl SOUČEK, Peter SLANINA, Kamila RÉBLOVÁ, Ondřej ZAPLETAL et. al.

Basic information

Original name

Myeloid lineage cells evince distinct steady-state level of certain gene groups in dependence on hereditary angioedema severity

Authors

BALLONOVÁ, Lucie (203 Czech Republic, belonging to the institution), Přemysl SOUČEK (203 Czech Republic, belonging to the institution), Peter SLANINA (703 Slovakia, belonging to the institution), Kamila RÉBLOVÁ (203 Czech Republic, belonging to the institution), Ondřej ZAPLETAL (203 Czech Republic, belonging to the institution), Marcela VLKOVÁ (203 Czech Republic, belonging to the institution), Roman HAKL (203 Czech Republic, belonging to the institution), Viktor BÍLY (703 Slovakia), Hana GROMBIŘÍKOVÁ (203 Czech Republic), Eliška SVOBODOVÁ (203 Czech Republic, belonging to the institution), Petra KULÍŠKOVÁ (203 Czech Republic, belonging to the institution), Julie ŠTÍCHOVÁ (203 Czech Republic, belonging to the institution), Marta SOBOTKOVÁ (203 Czech Republic), Zachová RADANA (203 Czech Republic), Jana HANZLÍKOVÁ (203 Czech Republic), Martina VACHOVÁ (203 Czech Republic), Pavlína KRÁLÍČKOVÁ (203 Czech Republic), Irena KRČMOVÁ (203 Czech Republic), Miloš JESEŇÁK (203 Czech Republic) and Tomáš FREIBERGER (203 Czech Republic, guarantor, belonging to the institution)

Edition

FRONTIERS IN GENETICS, LAUSANNE, FRONTIERS MEDIA SA, 2023, 1664-8021

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30101 Human genetics

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.700 in 2022

RIV identification code

RIV/00216224:14110/23:00131293

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3389/fgene.2023.1123914

UT WoS

001034532700001

Keywords in English

FXII; hereditary angioedema; immune cell; interferon-gamma; gene expression

Abstract

V originále

Hereditary angioedema (HAE) is a rare genetic disorder with variable expressivity even in carriers of the same underlying genetic defect, suggesting other genetic and epigenetic factors participate in modifying HAE severity. Recent knowledge indicates the role of immune cells in several aspects of HAE pathogenesis, which makes monocytes and macrophages candidates to mediate these effects. Here we combined a search for HAE phenotype modifying gene variants with the characterization of selected genes’ mRNA levels in monocyte and macrophages in a symptom-free period. While no such gene variant was found to be associated with a more severe or milder disease, patients revealed a higher number of dysregulated genes and their expression profile was significantly altered, which was typically manifested by changes in individual gene expression or by strengthened or weakened relations in mutually co-expressed gene groups, depending on HAE severity. SERPING1 showed decreased expression in HAE-C1INH patients, but this effect was significant only in patients carrying mutations supposedly activating nonsense-mediated decay. Pro-inflammatory CXC chemokine superfamily members CXCL8, 10 and 11 were downregulated, while other genes such as FCGR1A, or long non-coding RNA NEAT1 were upregulated in patients. Co-expression within some gene groups (such as an NF-kappaB function related group) was strengthened in patients with a severe and/or mild course compared to controls. All these findings show that transcript levels in myeloid cells achieve different activation or depression levels in HAE-C1INH patients than in healthy controls and/or based on disease severity and could participate in determining the HAE phenotype.

Links

MUNI/A/1098/2022, interní kód MU

Name: Nespecifická imunita u chorob imunitního systému

Investor: Masaryk University, Non-specific immunity in immune system diseases

MUNI/A/1244/2021, interní kód MU

Name: Vrozená imunita a její abnormality v rozvoji imunopatologických stavů

Investor: Masaryk University

NV18-05-00330, research and development project

Name: Genetická determinace závažnosti otoků podmíněných bradykininem u pacientů s hereditárním angioedémem

Investor: Ministry of Health of the CR, Genetic determination of bradykinin-mediated angioedema severity in patients with hereditary angioedema

90132, large research infrastructures

Name: NCMG II

Citovat

BALLONOVÁ, Lucie, Přemysl SOUČEK, Peter SLANINA, Kamila RÉBLOVÁ, Ondřej ZAPLETAL, Marcela VLKOVÁ, Roman HAKL, Viktor BÍLY, Hana GROMBIŘÍKOVÁ, Eliška SVOBODOVÁ, Petra KULÍŠKOVÁ, Julie ŠTÍCHOVÁ, Marta SOBOTKOVÁ, Zachová RADANA, Jana HANZLÍKOVÁ, Martina VACHOVÁ, Pavlína KRÁLÍČKOVÁ, Irena KRČMOVÁ, Miloš JESEŇÁK and Tomáš FREIBERGER. Myeloid lineage cells evince distinct steady-state level of certain gene groups in dependence on hereditary angioedema severity. FRONTIERS IN GENETICS. LAUSANNE: FRONTIERS MEDIA SA, 2023, vol. 14, July 2023, p. 1-15. ISSN 1664-8021. Available from: https://dx.doi.org/10.3389/fgene.2023.1123914.

@article{2298959,
   author = {Ballonová, Lucie and Souček, Přemysl and Slanina, Peter and Réblová, Kamila and Zapletal, Ondřej and Vlková, Marcela and Hakl, Roman and Bíly, Viktor and Grombiříková, Hana and Svobodová, Eliška and Kulíšková, Petra and Štíchová, Julie and Sobotková, Marta and Radana, Zachová and Hanzlíková, Jana and Vachová, Martina and Králíčková, Pavlína and Krčmová, Irena and Jeseňák, Miloš and Freiberger, Tomáš},
   article_location = {LAUSANNE},
   article_number = {July 2023},
   doi = {http://dx.doi.org/10.3389/fgene.2023.1123914},
   keywords = {FXII; hereditary angioedema; immune cell; interferon-gamma; gene expression},
   language = {eng},
   issn = {1664-8021},
   journal = {FRONTIERS IN GENETICS},
   title = {Myeloid lineage cells evince distinct steady-state level of certain gene groups in dependence on hereditary angioedema severity},
   url = {https://www.frontiersin.org/articles/10.3389/fgene.2023.1123914/full},
   volume = {14},
   year = {2023}
}

TY  - JOUR
ID  - 2298959
AU  - Ballonová, Lucie - Souček, Přemysl - Slanina, Peter - Réblová, Kamila - Zapletal, Ondřej - Vlková, Marcela - Hakl, Roman - Bíly, Viktor - Grombiříková, Hana - Svobodová, Eliška - Kulíšková, Petra - Štíchová, Julie - Sobotková, Marta - Radana, Zachová - Hanzlíková, Jana - Vachová, Martina - Králíčková, Pavlína - Krčmová, Irena - Jeseňák, Miloš - Freiberger, Tomáš
PY  - 2023
TI  - Myeloid lineage cells evince distinct steady-state level of certain gene groups in dependence on hereditary angioedema severity
JF  - FRONTIERS IN GENETICS
VL  - 14
IS  - July 2023
SP  - 1-15
EP  - 1-15
PB  - FRONTIERS MEDIA SA
SN  - 16648021
KW  - FXII
KW  - hereditary angioedema
KW  - immune cell
KW  - interferon-gamma
KW  - gene expression
UR  - https://www.frontiersin.org/articles/10.3389/fgene.2023.1123914/full
N2  - Hereditary angioedema (HAE) is a rare genetic disorder with variable expressivity even in carriers of the same underlying genetic defect, suggesting other genetic and epigenetic factors participate in modifying HAE severity. Recent knowledge indicates the role of immune cells in several aspects of HAE pathogenesis, which makes monocytes and macrophages candidates to mediate these effects. Here we combined a search for HAE phenotype modifying gene variants with the characterization of selected genes’ mRNA levels in monocyte and macrophages in a symptom-free period. While no such gene variant was found to be associated with a more severe or milder disease, patients revealed a higher number of dysregulated genes and their expression profile was significantly altered, which was typically manifested by changes in individual gene expression or by strengthened or weakened relations in mutually co-expressed gene groups, depending on HAE severity. SERPING1 showed decreased expression in HAE-C1INH patients, but this effect was significant only in patients carrying mutations supposedly activating nonsense-mediated decay. Pro-inflammatory CXC chemokine superfamily members CXCL8, 10 and 11 were downregulated, while other genes such as FCGR1A, or long non-coding RNA NEAT1 were upregulated in patients. Co-expression within some gene groups (such as an NF-kappaB function related group) was strengthened in patients with a severe and/or mild course compared to controls. All these findings show that transcript levels in myeloid cells achieve different activation or depression levels in HAE-C1INH patients than in healthy controls and/or based on disease severity and could participate in determining the HAE phenotype.
ER  -

BALLONOVÁ, Lucie, Přemysl SOUČEK, Peter SLANINA, Kamila RÉBLOVÁ, Ondřej ZAPLETAL, Marcela VLKOVÁ, Roman HAKL, Viktor BÍLY, Hana GROMBIŘÍKOVÁ, Eliška SVOBODOVÁ, Petra KULÍŠKOVÁ, Julie ŠTÍCHOVÁ, Marta SOBOTKOVÁ, Zachová RADANA, Jana HANZLÍKOVÁ, Martina VACHOVÁ, Pavlína KRÁLÍČKOVÁ, Irena KRČMOVÁ, Miloš JESEŇÁK and Tomáš FREIBERGER. Myeloid lineage cells evince distinct steady-state level of certain gene groups in dependence on hereditary angioedema severity. \textit{FRONTIERS IN GENETICS}. LAUSANNE: FRONTIERS MEDIA SA, 2023, vol.~14, July 2023, p.~1-15. ISSN~1664-8021. Available from: https://dx.doi.org/10.3389/fgene.2023.1123914.

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