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, vol. 11, No 6, p. 1-11. ISSN 2041-4889. doi:10.1038/s41419-020-2652-4. 2020.
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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
Original language English
Type of outcome Article in a journal
Field of Study 10601 Cell biology
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
WWW 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
Tags 14110114, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 10/8/2020 12:58.
Abstract
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.
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