Novel XIAP mutation causing enhanced spontaneous apoptosis and
disturbed NOD2 signalling in a patient with atypical
adult-onset Crohn's disease

J 2020

Novel XIAP mutation causing enhanced spontaneous apoptosis and disturbed NOD2 signalling in a patient with atypical adult-onset Crohn's disease

PARACKOVA, Zuzana, Tomas MILOTA, Petra VRABCOVA, Jitka SMETANOVA, Michael SVATON et. al.

Basic information

Original name

Novel XIAP mutation causing enhanced spontaneous apoptosis and disturbed NOD2 signalling in a patient with atypical adult-onset Crohn's disease

Authors

PARACKOVA, Zuzana (203 Czech Republic, guarantor), Tomas MILOTA (203 Czech Republic), Petra VRABCOVA (203 Czech Republic), Jitka SMETANOVA (203 Czech Republic), Michael SVATON (203 Czech Republic), Tomáš FREIBERGER (203 Czech Republic, belonging to the institution), Veronika KANDEROVA (203 Czech Republic) and Anna SEDIVA (203 Czech Republic)

Edition

CELL DEATH & DISEASE, LONDON, NATURE PUBLISHING GROUP, 2020, 2041-4889

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 8.469

RIV identification code

RIV/00216224:14110/20:00116174

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/s41419-020-2652-4

UT WoS

000552729800006

Keywords in English

X-LINKED INHIBITOR; CELL-DEATH; DEFICIENCY; ACTIVATION; KINASE; IAP

Abstract

V originále

X-linked inhibitor of apoptosis (XIAP) is the most potent human inhibitor of apoptosis, and is also involved in NOD2-dependent NF kappa B and MAPK signalling cascade activation. The absence or defective function of XIAP leads to the development of a rare and severe primary immunodeficiency known as X-linked lymphoproliferative syndrome type 2 (XLP-2), which is characterized by a triad of clinical manifestations, including a high incidence of haemophagocytic lymphohistiocytosis (HLH), lymphoproliferation and inflammatory bowel disease (IBD), usually with very early onset. Here, we present a novel XIAP mutation identified in a patient with atypical adult-onset IBD complicated by relapsing HLH, splenomegaly and sarcoid-like disease. The c.266delA mutation in the XIAP gene creates a premature stop codon, and causes a severe reduction in XIAP protein expression. The mutation is also associated with impaired spontaneous and staurosporine- and PMA-induced apoptosis accompanied by significantly increased expression of pro-apoptotic genes. We also confirmed the negative impact of this particular XIAP mutation on NOD2-dependent NF kappa B and MAPK activation, while NOD2-independent activation was found to be unaffected. Moreover, we assume that the mutation has an impact on the overproduction of IL-12 and IFN gamma, the shift towards the Th1 immune response and increased numbers of central memory and effector memory CD4+ and CD8+ T cells. All these changes contribute to immune dysregulation and the clinical manifestation of XLP-2.

Citovat

PARACKOVA, Zuzana, Tomas MILOTA, Petra VRABCOVA, Jitka SMETANOVA, Michael SVATON, Tomáš FREIBERGER, Veronika KANDEROVA and Anna SEDIVA. Novel XIAP mutation causing enhanced spontaneous apoptosis and disturbed NOD2 signalling in a patient with atypical adult-onset Crohn's disease. CELL DEATH & DISEASE. LONDON: NATURE PUBLISHING GROUP, 2020, vol. 11, No 6, p. 1-11. ISSN 2041-4889. Available from: https://dx.doi.org/10.1038/s41419-020-2652-4.

@article{1673768,
   author = {Parackova, Zuzana and Milota, Tomas and Vrabcova, Petra and Smetanova, Jitka and Svaton, Michael and Freiberger, Tomáš and Kanderova, Veronika and Sediva, Anna},
   article_location = {LONDON},
   article_number = {6},
   doi = {http://dx.doi.org/10.1038/s41419-020-2652-4},
   keywords = {X-LINKED INHIBITOR; CELL-DEATH; DEFICIENCY; ACTIVATION; KINASE; IAP},
   language = {eng},
   issn = {2041-4889},
   journal = {CELL DEATH & DISEASE},
   title = {Novel XIAP mutation causing enhanced spontaneous apoptosis and disturbed NOD2 signalling in a patient with atypical adult-onset Crohn's disease},
   url = {https://www.nature.com/articles/s41419-020-2652-4.pdf},
   volume = {11},
   year = {2020}
}

TY  - JOUR
ID  - 1673768
AU  - Parackova, Zuzana - Milota, Tomas - Vrabcova, Petra - Smetanova, Jitka - Svaton, Michael - Freiberger, Tomáš - Kanderova, Veronika - Sediva, Anna
PY  - 2020
TI  - Novel XIAP mutation causing enhanced spontaneous apoptosis and disturbed NOD2 signalling in a patient with atypical adult-onset Crohn's disease
JF  - CELL DEATH & DISEASE
VL  - 11
IS  - 6
SP  - 1-11
EP  - 1-11
PB  - NATURE PUBLISHING GROUP
SN  - 20414889
KW  - X-LINKED INHIBITOR
KW  - CELL-DEATH
KW  - DEFICIENCY
KW  - ACTIVATION
KW  - KINASE
KW  - IAP
UR  - https://www.nature.com/articles/s41419-020-2652-4.pdf
L2  - https://www.nature.com/articles/s41419-020-2652-4.pdf
N2  - X-linked inhibitor of apoptosis (XIAP) is the most potent human inhibitor of apoptosis, and is also involved in NOD2-dependent NF kappa B and MAPK signalling cascade activation. The absence or defective function of XIAP leads to the development of a rare and severe primary immunodeficiency known as X-linked lymphoproliferative syndrome type 2 (XLP-2), which is characterized by a triad of clinical manifestations, including a high incidence of haemophagocytic lymphohistiocytosis (HLH), lymphoproliferation and inflammatory bowel disease (IBD), usually with very early onset. Here, we present a novel XIAP mutation identified in a patient with atypical adult-onset IBD complicated by relapsing HLH, splenomegaly and sarcoid-like disease. The c.266delA mutation in the XIAP gene creates a premature stop codon, and causes a severe reduction in XIAP protein expression. The mutation is also associated with impaired spontaneous and staurosporine- and PMA-induced apoptosis accompanied by significantly increased expression of pro-apoptotic genes. We also confirmed the negative impact of this particular XIAP mutation on NOD2-dependent NF kappa B and MAPK activation, while NOD2-independent activation was found to be unaffected. Moreover, we assume that the mutation has an impact on the overproduction of IL-12 and IFN gamma, the shift towards the Th1 immune response and increased numbers of central memory and effector memory CD4+ and CD8+ T cells. All these changes contribute to immune dysregulation and the clinical manifestation of XLP-2.
ER  -

PARACKOVA, Zuzana, Tomas MILOTA, Petra VRABCOVA, Jitka SMETANOVA, Michael SVATON, Tomáš FREIBERGER, Veronika KANDEROVA and Anna SEDIVA. Novel XIAP mutation causing enhanced spontaneous apoptosis and disturbed NOD2 signalling in a patient with atypical adult-onset Crohn's disease. \textit{CELL DEATH \&{} DISEASE}. LONDON: NATURE PUBLISHING GROUP, 2020, vol.~11, No~6, p.~1-11. ISSN~2041-4889. Available from: https://dx.doi.org/10.1038/s41419-020-2652-4.

Detailed Information on Publication Record